rs6018199

Variant names:

• chr20-37381254-T-G
• rs6018199
• NM_198291.3:c.-172-1365T>G

Variant summary

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

The NM_198291.3(SRC):​c.-172-1365T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,094 control chromosomes in the GnomAD database, including 7,107 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 0.26 (7107 hom., cov: 31)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666
• Publications: 11 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, Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRC	NM_198291.3	c.-172-1365T>G		intron_variant	Intron 2 of 13	ENST00000373578.7	NP_938033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRC	ENST00000373578.7	c.-172-1365T>G		intron_variant	Intron 2 of 13	5	NM_198291.3	ENSP00000362680.2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39139 AN: 151976 Hom.: 7089 Cov.: 31

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.258 AC: 39189 AN: 152094 Hom.: 7107 Cov.: 31 AF XY: 0.253 AC XY: 18816 AN XY: 74352

African (AFR) AF: 0.521 AC: 21592 AN: 41454

American (AMR) AF: 0.156 AC: 2382 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3470

East Asian (EAS) AF: 0.184 AC: 951 AN: 5166

South Asian (SAS) AF: 0.106 AC: 510 AN: 4818

European-Finnish (FIN) AF: 0.165 AC: 1750 AN: 10594

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10739 AN: 67994

Other (OTH) AF: 0.232 AC: 490 AN: 2108

Alfa AF: 0.187 Hom.: 1922

Bravo AF: 0.268

Asia WGS AF: 0.189 AC: 656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.73
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs6018199; hg19: chr20-36009657;