chr20-37394136-T-C

Position:

• chr20-37394136-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.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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SRC	NM_198291.3	c.450-38T>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.450-38T>C		intron_variant		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

GnomAD3 exomes AF: 0.129 AC: 32426 AN: 250458 Hom.: 3402 AF XY: 0.123 AC XY: 16637 AN XY: 135350

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 SAS exome AF: 0.0824

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

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.0782

Gnomad4 ASJ exome AF: 0.0734

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.0795

Gnomad4 FIN exome AF: 0.0677

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.145

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

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.0810

Gnomad4 FIN AF: 0.0574

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.187

Alfa AF: 0.124 Hom.: 2439

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

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: rs6018257; hg19: chr20-36022539; COSMIC: COSV104672565; COSMIC: COSV104672565;