chr4-82426156-TAAGA-T

Variant names:

• chr4-82426156-TAAGA-T
• rs34583014
• NM_031372.4:c.1193-31_1193-28delTCTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_031372.4(HNRNPDL):​c.1193-31_1193-28delTCTT 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 (★). There are indicators that this mutation may affect the branch point..

• 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
• Publications: 4 publications found

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):

• muscular dystrophy, limb-girdle, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant limb-girdle muscular dystrophy type 1G

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031372.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPDL	NM_031372.4	MANE Select	c.1193-31_1193-28delTCTT		intron	N/A	NP_112740.1	O14979-1
	HNRNPDL	NM_001207000.1		c.1022-31_1022-28delTCTT		intron	N/A	NP_001193929.1	A0A087WUK2
	HNRNPDL	NR_003249.2		n.1728-31_1728-28delTCTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPDL	ENST00000295470.10	TSL:1 MANE Select	c.1193-31_1193-28delTCTT		intron	N/A	ENSP00000295470.5	O14979-1
	HNRNPDL	ENST00000621267.4	TSL:1	c.1193-31_1193-28delTCTT		intron	N/A	ENSP00000483254.1	O14979-1
	HNRNPDL	ENST00000614627.4	TSL:1	c.1022-31_1022-28delTCTT		intron	N/A	ENSP00000478723.1	A0A087WUK2

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

GnomAD2 exomes AF: 0.395 AC: 99139 AN: 250754 AF XY: 0.406

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 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

African (AFR) AF: 0.0937 AC: 3086 AN: 32948

American (AMR) AF: 0.497 AC: 22157 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 12505 AN: 25974

East Asian (EAS) AF: 0.175 AC: 6934 AN: 39546

South Asian (SAS) AF: 0.531 AC: 45533 AN: 85748

European-Finnish (FIN) AF: 0.428 AC: 22850 AN: 53382

Middle Eastern (MID) AF: 0.474 AC: 2704 AN: 5710

European-Non Finnish (NFE) AF: 0.390 AC: 424509 AN: 1089460

Other (OTH) AF: 0.392 AC: 23365 AN: 59542

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

African (AFR) AF: 0.102 AC: 4225 AN: 41540

American (AMR) AF: 0.473 AC: 7220 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1609 AN: 3462

East Asian (EAS) AF: 0.212 AC: 1101 AN: 5186

South Asian (SAS) AF: 0.548 AC: 2643 AN: 4826

European-Finnish (FIN) AF: 0.441 AC: 4638 AN: 10514

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.385 AC: 26130 AN: 67794

Other (OTH) AF: 0.358 AC: 755 AN: 2108

Alfa AF: 0.364 Hom.: 1987

Bravo AF: 0.309

Asia WGS AF: 0.381 AC: 1322 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8
BranchPoint Hunter		7.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34583014; hg19: chr4-83347309;