chr20-37400428-T-C

Position:

• chr20-37400428-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198291.3(SRC):​c.1039+134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 759,618 control chromosomes in the GnomAD database, including 9,798 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 0.20 (5422 hom., cov: 32)
  • Exomes 𝑓: 0.094 (4376 hom.)
• Consequence: SRC NM_198291.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.84

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRC	NM_198291.3	c.1039+134T>C		intron_variant		ENST00000373578.7	NP_938033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRC	ENST00000373578.7	c.1039+134T>C		intron_variant		5	NM_198291.3	ENSP00000362680	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29734 AN: 151886 Hom.: 5394 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0632

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.0944 AC: 57383 AN: 607614 Hom.: 4376 AF XY: 0.0924 AC XY: 28286 AN XY: 306014

Gnomad4 AFR exome AF: 0.484

Gnomad4 AMR exome AF: 0.0832

Gnomad4 ASJ exome AF: 0.0602

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.0689

Gnomad4 FIN exome AF: 0.0592

Gnomad4 NFE exome AF: 0.0783

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.196 AC: 29802 AN: 152004 Hom.: 5422 Cov.: 32 AF XY: 0.192 AC XY: 14293 AN XY: 74322

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0632

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.0768

Gnomad4 FIN AF: 0.0480

Gnomad4 NFE AF: 0.0822

Gnomad4 OTH AF: 0.175

Alfa AF: 0.102 Hom.: 1352

Bravo AF: 0.214

Asia WGS AF: 0.172 AC: 597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.020
DANN	Benign	0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1570209; hg19: chr20-36028831;