rs4982437

Positions:

• chr14-21248734-T-C

Variant summary

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

The NM_004500.4(HNRNPC):​c.-36-14505A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,194 control chromosomes in the GnomAD database, including 2,947 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 0.18 (2947 hom., cov: 31)
• Consequence: HNRNPC NM_004500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

HNRNPC (HGNC:5035): (heterogeneous nuclear ribonucleoprotein C) 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 can act as a tetramer and is involved in the assembly of 40S hnRNP particles. Multiple transcript variants encoding at least two different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPC	NM_004500.4	c.-36-14505A>G		intron_variant		ENST00000553300.6	NP_004491.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPC	ENST00000553300.6	c.-36-14505A>G		intron_variant		1	NM_004500.4	ENSP00000450544	P3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27617 AN: 152076 Hom.: 2926 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0851

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.182 AC: 27675 AN: 152194 Hom.: 2947 Cov.: 31 AF XY: 0.183 AC XY: 13631 AN XY: 74418

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0855

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.154

Alfa AF: 0.155 Hom.: 1018

Bravo AF: 0.193

Asia WGS AF: 0.128 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.97
DANN	Benign	0.43

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: rs4982437; hg19: chr14-21716893;