4-82427825-T-C

Position:

• chr4-82427825-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_031372.4(HNRNPDL):​c.774+193A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,138 control chromosomes in the GnomAD database, including 9,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (9817 hom., cov: 33)
• 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]

HNRNPDL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 4-82427825-T-C is Benign according to our data. Variant chr4-82427825-T-C is described in ClinVar as [Benign]. Clinvar id is 1222212.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPDL	NM_031372.4	c.774+193A>G		intron_variant		ENST00000295470.10	NP_112740.1
HNRNPDL	NM_001207000.1	c.774+193A>G		intron_variant			NP_001193929.1
HNRNPDL	NR_003249.2	n.1309+193A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPDL	ENST00000295470.10	c.774+193A>G		intron_variant		1	NM_031372.4	ENSP00000295470.5

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50291 AN: 152020 Hom.: 9812 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.366

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50320 AN: 152138 Hom.: 9817 Cov.: 33 AF XY: 0.339 AC XY: 25183 AN XY: 74350

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.365

Alfa AF: 0.391 Hom.: 16969

Bravo AF: 0.319

Asia WGS AF: 0.387 AC: 1343 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.25
DANN	Benign	0.57

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: rs6826022; hg19: chr4-83348978;