rs6124914

Variant names:

• chr20-37387840-T-C
• rs6124914
• NM_198291.3:c.350+1666T>C

Variant summary

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

The NM_198291.3(SRC):​c.350+1666T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 152,300 control chromosomes in the GnomAD database, including 284 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 0.033 (284 hom., cov: 33)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• 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: 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 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.350+1666T>C		intron	N/A	NP_938033.1
	SRC	NM_005417.5		c.350+1666T>C		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.350+1666T>C		intron	N/A	ENSP00000362680.2
	SRC	ENST00000358208.9	TSL:1	c.368+1363T>C		intron	N/A	ENSP00000350941.5
	SRC	ENST00000373567.6	TSL:1	c.350+1666T>C		intron	N/A	ENSP00000362668.2

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5069 AN: 152182 Hom.: 283 Cov.: 33

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.0281

Gnomad FIN AF: 0.00395

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00623

Gnomad OTH AF: 0.0315

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

GnomAD4 genome AF: 0.0333 AC: 5070 AN: 152300 Hom.: 284 Cov.: 33 AF XY: 0.0349 AC XY: 2600 AN XY: 74504

African (AFR) AF: 0.0632 AC: 2626 AN: 41554

American (AMR) AF: 0.0229 AC: 351 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1379 AN: 5182

South Asian (SAS) AF: 0.0275 AC: 133 AN: 4832

European-Finnish (FIN) AF: 0.00395 AC: 42 AN: 10632

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00622 AC: 423 AN: 68002

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0140 Hom.: 73

Bravo AF: 0.0360

Asia WGS AF: 0.142 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0070
DANN	Benign	0.24
PhyloP100		-1.6
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: rs6124914; hg19: chr20-36016243;