rs7141230

Variant names:

• chr14-21250580-C-T
• rs7141230
• NM_004500.4:c.-37+12731G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004500.4(HNRNPC):​c.-37+12731G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,024 control chromosomes in the GnomAD database, including 9,161 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 0.34 (9161 hom., cov: 32)
• Consequence: HNRNPC NM_004500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPC	NM_004500.4	c.-37+12731G>A		intron_variant	Intron 2 of 8	ENST00000553300.6	NP_004491.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPC	ENST00000553300.6	c.-37+12731G>A		intron_variant	Intron 2 of 8	1	NM_004500.4	ENSP00000450544.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52262 AN: 151908 Hom.: 9141 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.344 AC: 52317 AN: 152024 Hom.: 9161 Cov.: 32 AF XY: 0.347 AC XY: 25775 AN XY: 74298

African (AFR) AF: 0.337 AC: 13974 AN: 41450

American (AMR) AF: 0.390 AC: 5962 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 993 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1557 AN: 5172

South Asian (SAS) AF: 0.346 AC: 1669 AN: 4818

European-Finnish (FIN) AF: 0.359 AC: 3781 AN: 10546

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23302 AN: 67976

Other (OTH) AF: 0.316 AC: 669 AN: 2114

Alfa AF: 0.343 Hom.: 27448

Bravo AF: 0.344

Asia WGS AF: 0.350 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.55
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7141230; hg19: chr14-21718739;