Variant 4-82425953-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000507721.5(HNRNPDL):c.*106A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 888,944 control chromosomes in the GnomAD database, including 633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 84 hom., cov: 33)

Exomes 𝑓: 0.033 ( 549 hom. )

Consequence

HNRNPDL
ENST00000507721.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.494

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-82425953-T-C is Benign according to our data. Variant chr4-82425953-T-C is described in ClinVar as [Benign]. Clinvar id is 1284243.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0268 (4074/152274) while in subpopulation NFE AF= 0.0395 (2685/67996). AF 95% confidence interval is 0.0382. There are 84 homozygotes in gnomad4. There are 2010 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4074 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
HNRNPDL	NM_031372.4 linkuse as main transcript	c.*22+84A>G	intron_variant	ENST00000295470.10	NP_112740.1
HNRNPDL	NM_001207000.1 linkuse as main transcript	c.*22+84A>G	intron_variant		NP_001193929.1
HNRNPDL	NR_003249.2 linkuse as main transcript	n.1820+84A>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPDL	ENST00000295470.10 linkuse as main transcript	c.*22+84A>G		intron_variant		1	NM_031372.4	ENSP00000295470	P4	O14979-1

Frequencies

GnomAD3 genomes

AF:

0.0268

AC:

4075

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00656

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0188

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.0672

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0395

Gnomad OTH

AF:

0.0124

GnomAD4 exome

AF:

0.0331

AC:

24361

AN:

736670

Hom.:

549

Cov.:

AF XY:

0.0325

AC XY:

12576

AN XY:

386838

show subpopulations

Gnomad4 AFR exome

AF:

0.00540

Gnomad4 AMR exome

AF:

0.0148

Gnomad4 ASJ exome

AF:

0.0176

Gnomad4 EAS exome

AF:

0.0000849

Gnomad4 SAS exome

AF:

0.00756

Gnomad4 FIN exome

AF:

0.0624

Gnomad4 NFE exome

AF:

0.0396

Gnomad4 OTH exome

AF:

0.0296

GnomAD4 genome

AF:

0.0268

AC:

4074

AN:

152274

Hom.:

Cov.:

AF XY:

0.0270

AC XY:

2010

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00654

Gnomad4 AMR

AF:

0.0188

Gnomad4 ASJ

AF:

0.0133

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.0672

Gnomad4 NFE

AF:

0.0395

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0335

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over