rs527520007

Positions:

• chr4-82427311-AC-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_031372.4(HNRNPDL):​c.907-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000476 in 1,568,724 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: HNRNPDL NM_031372.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.464

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 4-82427311-AC-A is Benign according to our data. Variant chr4-82427311-AC-A is described in ClinVar as [Benign]. Clinvar id is 464393.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 422 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPDL	NM_031372.4	c.907-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000295470.10	NP_112740.1
HNRNPDL	NM_001207000.1	c.907-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001193929.1
HNRNPDL	NR_003249.2	n.1442-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPDL	ENST00000295470.10	c.907-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_031372.4	ENSP00000295470	P4

Frequencies

GnomAD3 genomes AF: 0.00273 AC: 416 AN: 152210 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00943

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000580 AC: 129 AN: 222602 Hom.: 0 AF XY: 0.000331 AC XY: 40 AN XY: 120814

Gnomad AFR exome AF: 0.00780

Gnomad AMR exome AF: 0.0000821

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000406

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000188

Gnomad OTH exome AF: 0.000371

GnomAD4 exome AF: 0.000229 AC: 325 AN: 1416396 Hom.: 0 Cov.: 27 AF XY: 0.000192 AC XY: 135 AN XY: 704100

Gnomad4 AFR exome AF: 0.00819

Gnomad4 AMR exome AF: 0.000118

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000507

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000825

Gnomad4 OTH exome AF: 0.000819

GnomAD4 genome AF: 0.00277 AC: 422 AN: 152328 Hom.: 1 Cov.: 33 AF XY: 0.00239 AC XY: 178 AN XY: 74494

Gnomad4 AFR AF: 0.00941

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.000218 Hom.: 0

Bravo AF: 0.00280

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant limb-girdle muscular dystrophy type 1G Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

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: rs527520007; hg19: chr4-83348464;