20-37400428-T-C

Variant names:

• chr20-37400428-T-C
• rs1570209
• NM_198291.3:c.1039+134T>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.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
• 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=-0.93).
• 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 rank	MANE	Protein	UniProt
SRC	NM_198291.3	c.1039+134T>C		intron_variant	Intron 10 of 13	ENST00000373578.7	NP_938033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRC	ENST00000373578.7	c.1039+134T>C		intron_variant	Intron 10 of 13	5	NM_198291.3	ENSP00000362680.2

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

African (AFR) AF: 0.484 AC: 6744 AN: 13936

American (AMR) AF: 0.0832 AC: 1158 AN: 13910

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 795 AN: 13202

East Asian (EAS) AF: 0.219 AC: 5867 AN: 26756

South Asian (SAS) AF: 0.0689 AC: 2528 AN: 36666

European-Finnish (FIN) AF: 0.0592 AC: 1534 AN: 25924

Middle Eastern (MID) AF: 0.127 AC: 272 AN: 2148

European-Non Finnish (NFE) AF: 0.0783 AC: 34895 AN: 445654

Other (OTH) AF: 0.122 AC: 3590 AN: 29418

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

African (AFR) AF: 0.480 AC: 19849 AN: 41364

American (AMR) AF: 0.109 AC: 1663 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0632 AC: 219 AN: 3464

East Asian (EAS) AF: 0.217 AC: 1119 AN: 5164

South Asian (SAS) AF: 0.0768 AC: 370 AN: 4818

European-Finnish (FIN) AF: 0.0480 AC: 509 AN: 10604

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0822 AC: 5586 AN: 67996

Other (OTH) AF: 0.175 AC: 370 AN: 2110

Alfa AF: 0.121 Hom.: 3023

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
PhyloP100		-3.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1570209; hg19: chr20-36028831;