rs6018256

Positions:

• chr20-37393751-T-C

Variant summary

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

The NM_198291.3(SRC):​c.351-144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 613,516 control chromosomes in the GnomAD database, including 9,303 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 0.20 (5249 hom., cov: 33)
  • Exomes 𝑓: 0.11 (4054 hom.)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

Genes affected

SRC (HGNC:11283): (SRC proto-oncogene, non-receptor tyrosine kinase) This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRC	NM_198291.3	c.351-144T>C		intron_variant		ENST00000373578.7	NP_938033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRC	ENST00000373578.7	c.351-144T>C		intron_variant		5	NM_198291.3	ENSP00000362680	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29802 AN: 151972 Hom.: 5220 Cov.: 33

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0872

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.108 AC: 49752 AN: 461426 Hom.: 4054 Cov.: 5 AF XY: 0.105 AC XY: 25378 AN XY: 241638

Gnomad4 AFR exome AF: 0.471

Gnomad4 AMR exome AF: 0.0858

Gnomad4 ASJ exome AF: 0.0635

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.0794

Gnomad4 FIN exome AF: 0.0614

Gnomad4 NFE exome AF: 0.0886

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.196 AC: 29872 AN: 152090 Hom.: 5249 Cov.: 33 AF XY: 0.192 AC XY: 14274 AN XY: 74348

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0651

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.0842

Gnomad4 FIN AF: 0.0491

Gnomad4 NFE AF: 0.0872

Gnomad4 OTH AF: 0.181

Alfa AF: 0.145 Hom.: 377

Bravo AF: 0.213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.022
DANN	Benign	0.46
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: rs6018256; hg19: chr20-36022154; COSMIC: COSV62439033; COSMIC: COSV62439033;