rs8016099

Variant names:

• chr14-21230910-A-C
• rs8016099
• NM_004500.4:c.317+87T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-21230910-A-C
• chr14-21230910-A-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004500.4(HNRNPC):​c.317+87T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,429,018 control chromosomes in the GnomAD database, including 45,417 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 0.21 (4035 hom., cov: 31)
  • Exomes 𝑓: 0.25 (41382 hom.)
• Consequence: HNRNPC NM_004500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPC	NM_004500.4	c.317+87T>G		intron_variant	Intron 4 of 8	ENST00000553300.6	NP_004491.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPC	ENST00000553300.6	c.317+87T>G		intron_variant	Intron 4 of 8	1	NM_004500.4	ENSP00000450544.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32443 AN: 151948 Hom.: 4028 Cov.: 31

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.263 AC: 62230 AN: 236738 AF XY: 0.262

Gnomad AFR exome AF: 0.0970

Gnomad AMR exome AF: 0.388

Gnomad ASJ exome AF: 0.235

Gnomad EAS exome AF: 0.301

Gnomad FIN exome AF: 0.223

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.249 AC: 318170 AN: 1276952 Hom.: 41382 Cov.: 17 AF XY: 0.250 AC XY: 160540 AN XY: 642784

African (AFR) AF: 0.0910 AC: 2672 AN: 29368

American (AMR) AF: 0.375 AC: 15204 AN: 40538

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 5614 AN: 24048

East Asian (EAS) AF: 0.283 AC: 10938 AN: 38662

South Asian (SAS) AF: 0.280 AC: 22157 AN: 79084

European-Finnish (FIN) AF: 0.223 AC: 11749 AN: 52728

Middle Eastern (MID) AF: 0.247 AC: 1313 AN: 5324

European-Non Finnish (NFE) AF: 0.248 AC: 235917 AN: 953116

Other (OTH) AF: 0.233 AC: 12606 AN: 54084

GnomAD4 genome AF: 0.213 AC: 32456 AN: 152066 Hom.: 4035 Cov.: 31 AF XY: 0.217 AC XY: 16138 AN XY: 74330

African (AFR) AF: 0.0962 AC: 3994 AN: 41516

American (AMR) AF: 0.317 AC: 4842 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3466

East Asian (EAS) AF: 0.300 AC: 1547 AN: 5158

South Asian (SAS) AF: 0.289 AC: 1392 AN: 4820

European-Finnish (FIN) AF: 0.214 AC: 2259 AN: 10580

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16838 AN: 67938

Other (OTH) AF: 0.209 AC: 440 AN: 2110

Alfa AF: 0.242 Hom.: 2742

Bravo AF: 0.216

Asia WGS AF: 0.293 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.79
PhyloP100		2.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
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: rs8016099; hg19: chr14-21699069; COSMIC: COSV60144243; COSMIC: COSV60144243;