dbSNP rs6018256: SRC:c.351-144T>C (chr20-37393751-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198291.3(SRC):c.351-144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 613,516 control chromosomes in the GnomAD database, including 9,303 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 ( 5249 hom., cov: 33)

Exomes 𝑓: 0.11 ( 4054 hom. )

Consequence

SRC
NM_198291.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.42

Publications

6 publications found

Variant links:

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)

SRC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRC	NM_198291.3 link	c.351-144T>C		intron_variant	Intron 5 of 13	ENST00000373578.7	NP_938033.1	P12931-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRC	ENST00000373578.7 link	c.351-144T>C		intron_variant	Intron 5 of 13	5	NM_198291.3	ENSP00000362680.2		P12931-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29802

AN:

151972

Hom.:

5220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0651

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.0850

Gnomad FIN

AF:

0.0491

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.0872

Gnomad OTH

AF:

0.181

GnomAD4 exome

AF:

0.108

AC:

49752

AN:

461426

Hom.:

4054

Cov.:

AF XY:

0.105

AC XY:

25378

AN XY:

241638

show subpopulations

African (AFR)

AF:

0.471

AC:

6111

AN:

12974

American (AMR)

AF:

0.0858

AC:

1763

AN:

20554

Ashkenazi Jewish (ASJ)

AF:

0.0635

AC:

880

AN:

13862

East Asian (EAS)

AF:

0.228

AC:

7073

AN:

31000

South Asian (SAS)

AF:

0.0794

AC:

3654

AN:

46040

European-Finnish (FIN)

AF:

0.0614

AC:

1963

AN:

31966

Middle Eastern (MID)

AF:

0.137

AC:

409

AN:

2976

European-Non Finnish (NFE)

AF:

0.0886

AC:

24419

AN:

275606

Other (OTH)

AF:

0.132

AC:

3480

AN:

26448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2155

4311

6466

8622

10777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

298

596

894

1192

1490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.196

AC:

29872

AN:

152090

Hom.:

5249

Cov.:

AF XY:

0.192

AC XY:

14274

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.469

AC:

19449

AN:

41454

American (AMR)

AF:

0.111

AC:

1705

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0651

AC:

226

AN:

3470

East Asian (EAS)

AF:

0.221

AC:

1138

AN:

5158

South Asian (SAS)

AF:

0.0842

AC:

406

AN:

4822

European-Finnish (FIN)

AF:

0.0491

AC:

521

AN:

10606

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0872

AC:

5928

AN:

67968

Other (OTH)

AF:

0.181

AC:

381

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1018

2036

3054

4072

5090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.145

Hom.:

377

Bravo

AF:

0.213

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.022

(source)

DANN

Benign

0.46

PhyloP100

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over