rs6018088

chr20-37370222-C-Achr20-37370222-C-G

Variant summary

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

The NM_198291.3(SRC):c.-173+4945C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,194 control chromosomes in the GnomAD database, including 4,821 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 (4821 hom., cov: 33)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRC	NM_198291.3	c.-173+4945C>A		intron_variant		ENST00000373578.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRC	ENST00000373578.7	c.-173+4945C>A		intron_variant		5	NM_198291.3	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32159 AN: 152076 Hom.: 4812 Cov.: 33

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.212 AC: 32191 AN: 152194 Hom.: 4821 Cov.: 33 AF XY: 0.208 AC XY: 15503 AN XY: 74410

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.0911

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.196

Alfa AF: 0.130 Hom.: 1925

Bravo AF: 0.219

Asia WGS AF: 0.167 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.9
Dann	Benign	0.37

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: rs6018088; hg19: chr20-35998625;