rs12106024

Positions:

• chr20-37350945-C-G
• chr20-37350945-C-T

Variant summary

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

The NM_198291.3(SRC):​c.-247+4690C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,104 control chromosomes in the GnomAD database, including 4,385 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 0.23 (4385 hom., cov: 32)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.48

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRC	NM_198291.3	c.-247+4690C>G		intron_variant		ENST00000373578.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRC	ENST00000373578.7	c.-247+4690C>G		intron_variant		5	NM_198291.3	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35662 AN: 151986 Hom.: 4374 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.235 AC: 35707 AN: 152104 Hom.: 4385 Cov.: 32 AF XY: 0.228 AC XY: 16964 AN XY: 74356

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.239

Alfa AF: 0.100 Hom.: 156

Bravo AF: 0.237

Asia WGS AF: 0.222 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.22

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: rs12106024; hg19: chr20-35979348;