rs10516673

chr4-82357640-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031370.3(HNRNPD):c.622-196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 422,184 control chromosomes in the GnomAD database, including 607 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (51 hom., cov: 33)
  • Exomes 𝑓: 0.028 (556 hom.)
• Consequence: HNRNPD NM_031370.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

Genes affected

HNRNPD (HGNC:5036): (heterogeneous nuclear ribonucleoprotein D) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are nucleic acid 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 repeats of quasi-RRM domains that bind to RNAs. It localizes to both the nucleus and the cytoplasm. This protein is implicated in the regulation of mRNA stability. Alternative splicing of this gene results in four transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPD	NM_031370.3	c.622-196A>G		intron_variant		ENST00000313899.12
HNRNPD	NM_001003810.2	c.565-196A>G		intron_variant
HNRNPD	NM_002138.4	c.622-196A>G		intron_variant
HNRNPD	NM_031369.3	c.565-196A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPD	ENST00000313899.12	c.622-196A>G		intron_variant		1	NM_031370.3	A1

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2047 AN: 152182 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00929

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.0285 AC: 7684 AN: 269884 Hom.: 556 Cov.: 5 AF XY: 0.0274 AC XY: 3824 AN XY: 139626

Gnomad4 AFR exome AF: 0.00227

Gnomad4 AMR exome AF: 0.0255

Gnomad4 ASJ exome AF: 0.00782

Gnomad4 EAS exome AF: 0.212

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.0297

Gnomad4 NFE exome AF: 0.00944

Gnomad4 OTH exome AF: 0.0186

GnomAD4 genome AF: 0.0135 AC: 2049 AN: 152300 Hom.: 51 Cov.: 33 AF XY: 0.0151 AC XY: 1125 AN XY: 74466

Gnomad4 AFR AF: 0.00257

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.0253

Gnomad4 NFE AF: 0.00931

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0101 Hom.: 5

Bravo AF: 0.0128

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.5
Dann	Benign	0.77

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: rs10516673; hg19: chr4-83278793;