20-37350945-C-G

Variant names:

• chr20-37350945-C-G
• rs12106024
• NM_198291.3:c.-247+4690C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, PanelApp Australia
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198291.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRC	NM_198291.3	MANE Select	c.-247+4690C>G		intron	N/A	NP_938033.1	P12931-1
	SRC	NM_005417.5		c.-247+6058C>G		intron	N/A	NP_005408.1	P12931-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRC	ENST00000373578.7	TSL:5 MANE Select	c.-247+4690C>G		intron	N/A	ENSP00000362680.2	P12931-1
	SRC	ENST00000497734.5	TSL:1	n.203+6058C>G		intron	N/A
	SRC	ENST00000876231.1		c.-247+5716C>G		intron	N/A	ENSP00000546290.1

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

African (AFR) AF: 0.260 AC: 10760 AN: 41450

American (AMR) AF: 0.178 AC: 2717 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3468

East Asian (EAS) AF: 0.187 AC: 970 AN: 5176

South Asian (SAS) AF: 0.220 AC: 1060 AN: 4828

European-Finnish (FIN) AF: 0.142 AC: 1504 AN: 10588

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17041 AN: 67984

Other (OTH) AF: 0.239 AC: 505 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.22
PhyloP100		-4.5
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: rs12106024; hg19: chr20-35979348;