rs6063022

Variant names:

• chr20-37364924-C-T
• rs6063022
• NM_198291.3:c.-246-280C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198291.3(SRC):​c.-246-280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,104 control chromosomes in the GnomAD database, including 2,315 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 0.17 (2315 hom., cov: 31)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 13 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRC	NM_198291.3	c.-246-280C>T		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.-246-280C>T		intron_variant	Intron 1 of 13	5	NM_198291.3	ENSP00000362680.2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25450 AN: 151986 Hom.: 2316 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.167 AC: 25475 AN: 152104 Hom.: 2315 Cov.: 31 AF XY: 0.163 AC XY: 12102 AN XY: 74356

African (AFR) AF: 0.221 AC: 9180 AN: 41482

American (AMR) AF: 0.141 AC: 2154 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 761 AN: 3472

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5172

South Asian (SAS) AF: 0.153 AC: 735 AN: 4810

European-Finnish (FIN) AF: 0.117 AC: 1242 AN: 10582

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10656 AN: 67990

Other (OTH) AF: 0.183 AC: 385 AN: 2108

Alfa AF: 0.160 Hom.: 6297

Bravo AF: 0.171

Asia WGS AF: 0.0700 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.78
PhyloP100		-0.11
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: rs6063022; hg19: chr20-35993327;