rs747182

Variant names:

• chr20-37354486-T-C
• rs747182
• NM_198291.3:c.-247+8231T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-37354486-T-C
• chr20-37354486-T-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+8231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,122 control chromosomes in the GnomAD database, including 1,989 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 0.16 (1989 hom., cov: 32)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 14 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: MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRC	NM_198291.3	c.-247+8231T>C		intron_variant	Intron 1 of 13	ENST00000373578.7	NP_938033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRC	ENST00000373578.7	c.-247+8231T>C		intron_variant	Intron 1 of 13	5	NM_198291.3	ENSP00000362680.2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23758 AN: 152004 Hom.: 1984 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.156 AC: 23774 AN: 152122 Hom.: 1989 Cov.: 32 AF XY: 0.155 AC XY: 11504 AN XY: 74370

African (AFR) AF: 0.199 AC: 8274 AN: 41476

American (AMR) AF: 0.119 AC: 1824 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3472

East Asian (EAS) AF: 0.188 AC: 973 AN: 5164

South Asian (SAS) AF: 0.203 AC: 980 AN: 4820

European-Finnish (FIN) AF: 0.105 AC: 1119 AN: 10608

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9441 AN: 67970

Other (OTH) AF: 0.179 AC: 379 AN: 2116

Alfa AF: 0.138 Hom.: 1248

Bravo AF: 0.159

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		-0.30
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: rs747182; hg19: chr20-35982889;