Genetic Variant ENST00000514325.1:n.1203A>G (chr4-82357640-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000514325.1(HNRNPD):n.1203A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 422,184 control chromosomes in the GnomAD database, including 607 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 51 hom., cov: 33)

Exomes 𝑓: 0.028 ( 556 hom. )

Consequence

HNRNPD
ENST00000514325.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.547

Publications

2 publications found

Variant links:

Genes affected

HNRNPD (HGNC:5036): (heterogeneous nuclear ribonucleoprotein D) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are nucleic acid 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 repeats of quasi-RRM domains that bind to RNAs. It localizes to both the nucleus and the cytoplasm. This protein is implicated in the regulation of mRNA stability. Alternative splicing of this gene results in four transcript variants. [provided by RefSeq, Jul 2008]

HNRNPD Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P

HNRNPD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HNRNPD	NM_031370.3 link	c.622-196A>G	intron_variant	Intron 4 of 8	ENST00000313899.12	NP_112738.1	Q14103-1A1LU37
HNRNPD	NM_031369.3 link	c.565-196A>G	intron_variant	Intron 3 of 7		NP_112737.1	Q14103-2A0A024RDB4
HNRNPD	NM_002138.4 link	c.622-196A>G	intron_variant	Intron 4 of 7		NP_002129.2	Q14103-3A0A024RDF4
HNRNPD	NM_001003810.2 link	c.565-196A>G	intron_variant	Intron 3 of 6		NP_001003810.1	Q14103-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPD	ENST00000313899.12 link	c.622-196A>G		intron_variant	Intron 4 of 8	1	NM_031370.3	ENSP00000313199.7		Q14103-1

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2047

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0220

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.0162

Gnomad FIN

AF:

0.0253

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00929

Gnomad OTH

AF:

0.0139

GnomAD4 exome

AF:

0.0285

AC:

7684

AN:

269884

Hom.:

556

Cov.:

AF XY:

0.0274

AC XY:

3824

AN XY:

139626

show subpopulations

African (AFR)

AF:

0.00227

AC:

AN:

7504

American (AMR)

AF:

0.0255

AC:

232

AN:

9092

Ashkenazi Jewish (ASJ)

AF:

0.00782

AC:

AN:

9334

East Asian (EAS)

AF:

0.212

AC:

4642

AN:

21858

South Asian (SAS)

AF:

0.0166

AC:

192

AN:

11588

European-Finnish (FIN)

AF:

0.0297

AC:

561

AN:

18916

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

1288

European-Non Finnish (NFE)

AF:

0.00944

AC:

1638

AN:

173428

Other (OTH)

AF:

0.0186

AC:

314

AN:

16876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

304

608

912

1216

1520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.0135

AC:

2049

AN:

152300

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1125

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00257

AC:

107

AN:

41574

American (AMR)

AF:

0.0220

AC:

336

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00893

AC:

AN:

3472

East Asian (EAS)

AF:

0.108

AC:

562

AN:

5182

South Asian (SAS)

AF:

0.0168

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0253

AC:

269

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00931

AC:

633

AN:

68026

Other (OTH)

AF:

0.0123

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

102

204

305

407

509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0101

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.5

(source)

DANN

Benign

0.77

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over