rs61737724

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_031372.4(HNRNPDL):c.81C>T(p.Leu27Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,379,782 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 55 hom., cov: 32)

Exomes 𝑓: 0.028 ( 497 hom. )

Consequence

HNRNPDL
NM_031372.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.234

Publications

2 publications found

Variant links:

Genes affected

HNRNPDL (HGNC:5037): (heterogeneous nuclear ribonucleoprotein D like) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two RRM domains that bind to RNAs. Three alternatively spliced transcript variants have been described for this gene. One of the variants is probably not translated because the transcript is a candidate for nonsense-mediated mRNA decay. The protein isoforms encoded by this gene are similar to its family member HNRPD. [provided by RefSeq, May 2011]

HNRNPDL Gene-Disease associations (from GenCC):

autosomal dominant limb-girdle muscular dystrophy type 1G
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
muscular dystrophy, limb-girdle, autosomal dominant
Inheritance: AD Classification: MODERATE Submitted by: ClinGen

HNRNPDL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 4-82429610-G-A is Benign according to our data. Variant chr4-82429610-G-A is described in ClinVar as Benign. ClinVar VariationId is 464391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.234 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0208 (3151/151632) while in subpopulation NFE AF = 0.0322 (2179/67768). AF 95% confidence interval is 0.031. There are 55 homozygotes in GnomAd4. There are 1441 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3151 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPDL	NM_031372.4 link	c.81C>T	p.Leu27Leu	synonymous_variant	Exon 1 of 8	ENST00000295470.10	NP_112740.1	O14979-1A0A024RDB5
HNRNPDL	NM_001207000.1 link	c.81C>T	p.Leu27Leu	synonymous_variant	Exon 1 of 7		NP_001193929.1	O14979A0A087WUK2
HNRNPDL	NR_003249.2 link	n.616C>T		non_coding_transcript_exon_variant	Exon 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPDL	ENST00000295470.10 link	c.81C>T	p.Leu27Leu	synonymous_variant	Exon 1 of 8	1	NM_031372.4	ENSP00000295470.5		O14979-1

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3154

AN:

151518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00591

Gnomad AMI

AF:

0.00331

Gnomad AMR

AF:

0.0304

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00519

Gnomad FIN

AF:

0.00946

Gnomad MID

AF:

0.0581

Gnomad NFE

AF:

0.0322

Gnomad OTH

AF:

0.0322

GnomAD2 exomes

AF:

0.0217

AC:

389

AN:

17890

AF XY:

0.0201

show subpopulations

Gnomad AFR exome

AF:

0.00888

Gnomad AMR exome

AF:

0.0267

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00587

Gnomad NFE exome

AF:

0.0412

Gnomad OTH exome

AF:

0.0392

GnomAD4 exome

AF:

0.0279

AC:

34307

AN:

1228150

Hom.:

497

Cov.:

AF XY:

0.0276

AC XY:

16407

AN XY:

595196

show subpopulations

African (AFR)

AF:

0.00407

AC:

AN:

23576

American (AMR)

AF:

0.0260

AC:

268

AN:

10318

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

241

AN:

16692

East Asian (EAS)

AF:

0.00

AC:

AN:

28206

South Asian (SAS)

AF:

0.00661

AC:

354

AN:

53516

European-Finnish (FIN)

AF:

0.00828

AC:

334

AN:

40328

Middle Eastern (MID)

AF:

0.0344

AC:

125

AN:

3638

European-Non Finnish (NFE)

AF:

0.0316

AC:

31608

AN:

1001738

Other (OTH)

AF:

0.0255

AC:

1281

AN:

50138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1873

3747

5620

7494

9367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1244

2488

3732

4976

6220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0208

AC:

3151

AN:

151632

Hom.:

Cov.:

AF XY:

0.0194

AC XY:

1441

AN XY:

74114

show subpopulations

African (AFR)

AF:

0.00589

AC:

244

AN:

41410

American (AMR)

AF:

0.0303

AC:

463

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5032

South Asian (SAS)

AF:

0.00499

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00946

AC:

100

AN:

10568

Middle Eastern (MID)

AF:

0.0625

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0322

AC:

2179

AN:

67768

Other (OTH)

AF:

0.0318

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

158

316

474

632

790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0220

Hom.:

Bravo

AF:

0.0231

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal dominant limb-girdle muscular dystrophy type 1G

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.0

(source)

DANN

Benign

0.96

PhyloP100

0.23

PromoterAI

-0.033

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over