rs6017944

Variant names:

• chr20-37349168-A-G
• rs6017944
• NM_198291.3:c.-247+2913A>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+2913A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,116 control chromosomes in the GnomAD database, including 6,532 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 0.27 (6532 hom., cov: 32)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRC	NM_198291.3	MANE Select	c.-247+2913A>G		intron	N/A	NP_938033.1
	SRC	NM_005417.5		c.-247+4281A>G		intron	N/A	NP_005408.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRC	ENST00000373578.7	TSL:5 MANE Select	c.-247+2913A>G		intron	N/A	ENSP00000362680.2
	SRC	ENST00000497734.5	TSL:1	n.203+4281A>G		intron	N/A
	SRC	ENST00000692112.1		c.-247+1932A>G		intron	N/A	ENSP00000508666.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41476 AN: 151998 Hom.: 6531 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.00866

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.273 AC: 41506 AN: 152116 Hom.: 6532 Cov.: 32 AF XY: 0.266 AC XY: 19807 AN XY: 74362

African (AFR) AF: 0.416 AC: 17230 AN: 41454

American (AMR) AF: 0.186 AC: 2843 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.00868 AC: 45 AN: 5186

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4822

European-Finnish (FIN) AF: 0.156 AC: 1655 AN: 10602

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17022 AN: 67970

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.275 Hom.: 922

Bravo AF: 0.281

Asia WGS AF: 0.124 AC: 438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.20
PhyloP100		0.12
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: rs6017944; hg19: chr20-35977571;