dbSNP rs6094509: SRC:c.-172-5747A>G (chr20-37376872-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_198291.3(SRC):c.-172-5747A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,110 control chromosomes in the GnomAD database, including 6,407 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 0.26 ( 6407 hom., cov: 32)

Consequence

SRC
NM_198291.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.488

Publications

4 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: 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)

SRC links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_198291.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 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.-172-5747A>G		intron	N/A	NP_938033.1	P12931-1
	SRC	NM_005417.5		c.-172-5747A>G		intron	N/A	NP_005408.1	P12931-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SRC	ENST00000373578.7	TSL:5 MANE Select	c.-172-5747A>G	intron	N/A	ENSP00000362680.2	P12931-1
SRC	ENST00000497734.5	TSL:1	n.278-5747A>G	intron	N/A
SRC	ENST00000876231.1		c.-172-5747A>G	intron	N/A	ENSP00000546290.1

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39243

AN:

151992

Hom.:

6391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.246

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

GnomAD4 genome

AF:

0.258

AC:

39290

AN:

152110

Hom.:

6407

Cov.:

AF XY:

0.253

AC XY:

18833

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.469

AC:

19462

AN:

41482

American (AMR)

AF:

0.167

AC:

2557

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

669

AN:

3470

East Asian (EAS)

AF:

0.185

AC:

960

AN:

5176

South Asian (SAS)

AF:

0.109

AC:

524

AN:

4824

European-Finnish (FIN)

AF:

0.173

AC:

1835

AN:

10580

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12543

AN:

67982

Other (OTH)

AF:

0.242

AC:

510

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1419

2838

4258

5677

7096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.202

Hom.:

6012

Bravo

AF:

0.268

Asia WGS

AF:

0.187

AC:

650

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.8

(source)

DANN

Benign

0.51

PhyloP100

-0.49

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over