Genetic Variant SRF:c.*1502C>T (chr6-43180692-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003131.4(SRF):c.*1502C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 152,600 control chromosomes in the GnomAD database, including 1,044 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 0.095 ( 1044 hom., cov: 32)

Exomes 𝑓: 0.064 ( 0 hom. )

Consequence

SRF
NM_003131.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.913

Publications

8 publications found

Variant links:

Genes affected

SRF (HGNC:11291): (serum response factor) This gene encodes a ubiquitous nuclear protein that stimulates both cell proliferation and differentiation. It is a member of the MADS (MCM1, Agamous, Deficiens, and SRF) box superfamily of transcription factors. This protein binds to the serum response element (SRE) in the promoter region of target genes. This protein regulates the activity of many immediate-early genes, for example c-fos, and thereby participates in cell cycle regulation, apoptosis, cell growth, and cell differentiation. This gene is the downstream target of many pathways; for example, the mitogen-activated protein kinase pathway (MAPK) that acts through the ternary complex factors (TCFs). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

SRF links:

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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=-0.47).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003131.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRF	NM_003131.4	MANE Select	c.*1502C>T		3_prime_UTR	Exon 7 of 7	NP_003122.1
	SRF	NM_001292001.2		c.*1502C>T		3_prime_UTR	Exon 7 of 7	NP_001278930.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRF	ENST00000265354.6	TSL:1 MANE Select	c.*1502C>T		3_prime_UTR	Exon 7 of 7	ENSP00000265354.4

Frequencies

GnomAD3 genomes

AF:

0.0949

AC:

14426

AN:

152058

Hom.:

1041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.0634

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0540

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0472

Gnomad OTH

AF:

0.0894

GnomAD4 exome

AF:

0.0637

AC:

AN:

424

Hom.:

Cov.:

AF XY:

0.0606

AC XY:

AN XY:

264

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0677

AC:

AN:

384

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0333

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0950

AC:

14450

AN:

152176

Hom.:

1044

Cov.:

AF XY:

0.0980

AC XY:

7288

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.136

AC:

5661

AN:

41490

American (AMR)

AF:

0.126

AC:

1931

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

220

AN:

3472

East Asian (EAS)

AF:

0.362

AC:

1870

AN:

5170

South Asian (SAS)

AF:

0.158

AC:

762

AN:

4828

European-Finnish (FIN)

AF:

0.0540

AC:

573

AN:

10608

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0472

AC:

3212

AN:

68004

Other (OTH)

AF:

0.0946

AC:

200

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

625

1249

1874

2498

3123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.0676

Hom.:

115

Bravo

AF:

0.104

Asia WGS

AF:

0.238

AC:

829

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.91

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over