20-37394136-T-C

Variant names:

• chr20-37394136-T-C
• rs6018257
• NM_198291.3:c.450-38T>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.450-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,594,328 control chromosomes in the GnomAD database, including 19,066 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 (5603 hom., cov: 33)
  • Exomes 𝑓: 0.12 (13463 hom.)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416
• Publications: 22 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRC	NM_198291.3	c.450-38T>C		intron_variant	Intron 6 of 13	ENST00000373578.7	NP_938033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRC	ENST00000373578.7	c.450-38T>C		intron_variant	Intron 6 of 13	5	NM_198291.3	ENSP00000362680.2

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32207 AN: 152060 Hom.: 5574 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0817

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.129 AC: 32426 AN: 250458 AF XY: 0.123

Gnomad AFR exome AF: 0.484

Gnomad AMR exome AF: 0.0717

Gnomad ASJ exome AF: 0.0719

Gnomad EAS exome AF: 0.220

Gnomad FIN exome AF: 0.0633

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.121 AC: 174071 AN: 1442148 Hom.: 13463 Cov.: 27 AF XY: 0.118 AC XY: 85146 AN XY: 718578

African (AFR) AF: 0.485 AC: 16077 AN: 33136

American (AMR) AF: 0.0782 AC: 3494 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0734 AC: 1908 AN: 25996

East Asian (EAS) AF: 0.222 AC: 8779 AN: 39588

South Asian (SAS) AF: 0.0795 AC: 6818 AN: 85802

European-Finnish (FIN) AF: 0.0677 AC: 3580 AN: 52900

Middle Eastern (MID) AF: 0.137 AC: 787 AN: 5738

European-Non Finnish (NFE) AF: 0.113 AC: 123997 AN: 1094586

Other (OTH) AF: 0.145 AC: 8631 AN: 59712

GnomAD4 genome AF: 0.212 AC: 32278 AN: 152180 Hom.: 5603 Cov.: 33 AF XY: 0.207 AC XY: 15396 AN XY: 74422

African (AFR) AF: 0.475 AC: 19716 AN: 41496

American (AMR) AF: 0.125 AC: 1915 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1124 AN: 5176

South Asian (SAS) AF: 0.0810 AC: 391 AN: 4828

European-Finnish (FIN) AF: 0.0574 AC: 609 AN: 10610

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

European-Non Finnish (NFE) AF: 0.114 AC: 7718 AN: 67998

Other (OTH) AF: 0.187 AC: 396 AN: 2114

Alfa AF: 0.133 Hom.: 4691

Bravo AF: 0.228

Asia WGS AF: 0.175 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.18
DANN	Benign	0.53
PhyloP100		-0.42
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: rs6018257; hg19: chr20-36022539; COSMIC: COSV104672565; COSMIC: COSV104672565;