rs6018256

Variant names:

• chr20-37393751-T-C
• rs6018256
• NM_198291.3:c.351-144T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

SRC Gene-Disease associations (from GenCC):

• thrombocytopenia 6

  Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• colorectal cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198291.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRC	NM_198291.3	MANE Select	c.351-144T>C		intron	N/A	NP_938033.1	P12931-1
	SRC	NM_005417.5		c.351-144T>C		intron	N/A	NP_005408.1	P12931-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRC	ENST00000373578.7	TSL:5 MANE Select	c.351-144T>C		intron	N/A	ENSP00000362680.2	P12931-1
	SRC	ENST00000358208.9	TSL:1	c.402-144T>C		intron	N/A	ENSP00000350941.5	P12931-3
	SRC	ENST00000373567.6	TSL:1	c.351-144T>C		intron	N/A	ENSP00000362668.2	P12931-1

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

African (AFR) AF: 0.471 AC: 6111 AN: 12974

American (AMR) AF: 0.0858 AC: 1763 AN: 20554

Ashkenazi Jewish (ASJ) AF: 0.0635 AC: 880 AN: 13862

East Asian (EAS) AF: 0.228 AC: 7073 AN: 31000

South Asian (SAS) AF: 0.0794 AC: 3654 AN: 46040

European-Finnish (FIN) AF: 0.0614 AC: 1963 AN: 31966

Middle Eastern (MID) AF: 0.137 AC: 409 AN: 2976

European-Non Finnish (NFE) AF: 0.0886 AC: 24419 AN: 275606

Other (OTH) AF: 0.132 AC: 3480 AN: 26448

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

African (AFR) AF: 0.469 AC: 19449 AN: 41454

American (AMR) AF: 0.111 AC: 1705 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 226 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1138 AN: 5158

South Asian (SAS) AF: 0.0842 AC: 406 AN: 4822

European-Finnish (FIN) AF: 0.0491 AC: 521 AN: 10606

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0872 AC: 5928 AN: 67968

Other (OTH) AF: 0.181 AC: 381 AN: 2108

Alfa AF: 0.145 Hom.: 377

Bravo AF: 0.213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.022
DANN	Benign	0.46
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs6018256; hg19: chr20-36022154; COSMIC: COSV62439033; COSMIC: COSV62439033;