7-37909680-C-T

Position:

chr7-37909680-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP7BS1_SupportingBS2

The NM_003014.4(SFRP4):c.792G>A(p.Arg264=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00097 in 1,562,410 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 4 hom. )

Consequence

SFRP4
NM_003014.4 splice_region, synonymous

Scores

Splicing: ADA: 0.03078

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.274

Variant links:

Genes affected

SFRP4 (HGNC:10778): (secreted frizzled related protein 4) Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression. [provided by RefSeq, Jul 2008]

SFRP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP7

Synonymous conserved (PhyloP=0.274 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000612 (93/152000) while in subpopulation NFE AF= 0.000913 (62/67924). AF 95% confidence interval is 0.00073. There are 0 homozygotes in gnomad4. There are 33 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFRP4	NM_003014.4 linkuse as main transcript	c.792G>A	p.Arg264=	splice_region_variant, synonymous_variant	5/6	ENST00000436072.7	NP_003005.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SFRP4	ENST00000436072.7 linkuse as main transcript	c.792G>A	p.Arg264=	splice_region_variant, synonymous_variant	5/6	1	NM_003014.4	ENSP00000410715	P1
SFRP4	ENST00000447200.2 linkuse as main transcript	c.390G>A	p.Arg130=	splice_region_variant, synonymous_variant	6/6	5		ENSP00000402262
SFRP4	ENST00000478975.1 linkuse as main transcript	n.160G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000612

AC:

AN:

151884

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000948

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000913

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.000718

AC:

165

AN:

229684

Hom.:

AF XY:

0.000755

AC XY:

AN XY:

124422

show subpopulations

Gnomad AFR exome

AF:

0.000334

Gnomad AMR exome

AF:

0.000172

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000860

Gnomad FIN exome

AF:

0.000751

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.000555

GnomAD4 exome

AF:

0.00101

AC:

1422

AN:

1410410

Hom.:

Cov.:

AF XY:

0.000979

AC XY:

687

AN XY:

701878

show subpopulations

Gnomad4 AFR exome

AF:

0.0000949

Gnomad4 AMR exome

AF:

0.000174

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00119

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.000807

GnomAD4 genome

AF:

0.000612

AC:

AN:

152000

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.000948

Gnomad4 NFE

AF:

0.000913

Gnomad4 OTH

AF:

0.000952

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000665

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 26, 2022

This sequence change affects codon 264 of the SFRP4 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SFRP4 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs147388554, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SFRP4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1525259). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.031

dbscSNV1_RF

Benign

0.32

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over