NM_198291.3:c.-246-6954G>A

Variant names:

• chr20-37358250-G-A
• rs6017996
• NM_198291.3:c.-246-6954G>A

Variant summary

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

The NM_198291.3(SRC):​c.-246-6954G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,136 control chromosomes in the GnomAD database, including 7,168 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 0.25 (7168 hom., cov: 32)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.526 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.-246-6954G>A		intron	N/A	NP_938033.1	P12931-1
	SRC	NM_005417.5		c.-246-6954G>A		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.-246-6954G>A		intron	N/A	ENSP00000362680.2	P12931-1
	SRC	ENST00000497734.5	TSL:1	n.204-6954G>A		intron	N/A
	SRC	ENST00000876231.1		c.-246-6954G>A		intron	N/A	ENSP00000546290.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37526 AN: 152018 Hom.: 7148 Cov.: 32

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.247 AC: 37591 AN: 152136 Hom.: 7168 Cov.: 32 AF XY: 0.240 AC XY: 17851 AN XY: 74396

African (AFR) AF: 0.532 AC: 22036 AN: 41454

American (AMR) AF: 0.158 AC: 2410 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 804 AN: 3470

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5186

South Asian (SAS) AF: 0.178 AC: 857 AN: 4824

European-Finnish (FIN) AF: 0.0670 AC: 710 AN: 10604

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10047 AN: 67990

Other (OTH) AF: 0.241 AC: 509 AN: 2110

Alfa AF: 0.184 Hom.: 6564

Bravo AF: 0.265

Asia WGS AF: 0.120 AC: 419 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	0.082
DANN	Benign	0.77
PhyloP100		-1.1
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: rs6017996; hg19: chr20-35986653;