4-82426156-TAAGA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_031372.4(HNRNPDL):c.1193-31_1193-28del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,588,816 control chromosomes in the GnomAD database, including 124,763 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (9509 hom., cov: 0)
  • Exomes 𝑓: 0.39 (115254 hom.)
• Consequence: HNRNPDL NM_031372.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.85

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-82426156-TAAGA-T is Benign according to our data. Variant chr4-82426156-TAAGA-T is described in ClinVar as [Benign]. Clinvar id is 1228006.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPDL	NM_031372.4	c.1193-31_1193-28del		intron_variant		ENST00000295470.10
HNRNPDL	NM_001207000.1	c.1022-31_1022-28del		intron_variant
HNRNPDL	NR_003249.2	n.1728-31_1728-28del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPDL	ENST00000295470.10	c.1193-31_1193-28del		intron_variant		1	NM_031372.4	P4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48785 AN: 151764 Hom.: 9505 Cov.: 0

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.359

GnomAD3 exomes AF: 0.395 AC: 99139 AN: 250754 Hom.: 21163 AF XY: 0.406 AC XY: 54983 AN XY: 135542

Gnomad AFR exome AF: 0.0922

Gnomad AMR exome AF: 0.497

Gnomad ASJ exome AF: 0.469

Gnomad EAS exome AF: 0.215

Gnomad SAS exome AF: 0.538

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.384

Gnomad OTH exome AF: 0.422

GnomAD4 exome AF: 0.392 AC: 563643 AN: 1436934 Hom.: 115254 AF XY: 0.397 AC XY: 284485 AN XY: 716670

Gnomad4 AFR exome AF: 0.0937

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.392

GnomAD4 genome AF: 0.321 AC: 48796 AN: 151882 Hom.: 9509 Cov.: 0 AF XY: 0.329 AC XY: 24443 AN XY: 74222

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.358

Alfa AF: 0.364 Hom.: 1987

Bravo AF: 0.309

Asia WGS AF: 0.381 AC: 1322 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs34583014; hg19: chr4-83347309;