rs6094509

Positions:

• chr20-37376872-A-G

Variant summary

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

The NM_198291.3(SRC):​c.-172-5747A>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 152,110 control chromosomes in the GnomAD database, including 6,407 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 (6407 hom., cov: 32)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

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=-0.94).
• 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.-172-5747A>G		intron_variant		ENST00000373578.7	NP_938033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRC	ENST00000373578.7	c.-172-5747A>G		intron_variant		5	NM_198291.3	ENSP00000362680	P1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39243 AN: 151992 Hom.: 6391 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.258 AC: 39290 AN: 152110 Hom.: 6407 Cov.: 32 AF XY: 0.253 AC XY: 18833 AN XY: 74354

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.242

Alfa AF: 0.194 Hom.: 4214

Bravo AF: 0.268

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.51

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: rs6094509; hg19: chr20-36005275;