4-82425953-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.494

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 -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 GnomAd at 4075 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPDL	NM_031372.4	c.*22+84A>G		intron_variant		ENST00000295470.10
HNRNPDL	NM_001207000.1	c.*22+84A>G		intron_variant
HNRNPDL	NR_003249.2	n.1820+84A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPDL	ENST00000295470.10	c.*22+84A>G		intron_variant		1	NM_031372.4	P4

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4075 AN: 152156 Hom.: 84 Cov.: 33

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.: 10 AF XY: 0.0325 AC XY: 12576 AN XY: 386838

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.: 84 Cov.: 33 AF XY: 0.0270 AC XY: 2010 AN XY: 74454

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.: 23

Bravo AF: 0.0220

Asia WGS AF: 0.00433 AC: 15 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 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	13
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

Other links and lift over

dbSNP: rs10026631; hg19: chr4-83347106;