Variant 7-37909611-A-ACTTACTATGGATCTTTTACTAAGCTGATCTCTCCATTTTTCAAC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003014.4(SFRP4):c.855+5_855+6insGTTGAAAAATGGAGAGATCAGCTTAGTAAAAGATCCATAGTAAG variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,534,502 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

SFRP4
NM_003014.4 splice_donor_region, intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFRP4	NM_003014.4 linkuse as main transcript	c.855+5_855+6insGTTGAAAAATGGAGAGATCAGCTTAGTAAAAGATCCATAGTAAG		splice_donor_region_variant, intron_variant		ENST00000436072.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
SFRP4	ENST00000436072.7 linkuse as main transcript	c.855+5_855+6insGTTGAAAAATGGAGAGATCAGCTTAGTAAAAGATCCATAGTAAG	splice_donor_region_variant, intron_variant	1	NM_003014.4	P1
SFRP4	ENST00000478975.1 linkuse as main transcript	n.223+5_223+6insGTTGAAAAATGGAGAGATCAGCTTAGTAAAAGATCCATAGTAAG	splice_donor_region_variant, intron_variant, non_coding_transcript_variant	2
SFRP4	ENST00000447200.2 linkuse as main transcript		downstream_gene_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000447

AC:

AN:

223622

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121466

show subpopulations

Gnomad AFR exome

AF:

0.0000700

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1382338

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688800

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000283

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

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

Invitae

Sep 07, 2022

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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with SFRP4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change falls in intron 5 of the SFRP4 gene. It does not directly change the encoded amino acid sequence of the SFRP4 protein. It affects a nucleotide within the consensus splice site. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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