Genetic Variant SFRP4:c.-256C>G (chr7-37916793-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003014.4(SFRP4):c.-256C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SFRP4
NM_003014.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.477

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

Pyle disease
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

SFRP4 links:

ENSG00000290149 (HGNC:):

ENSG00000290149 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFRP4	NM_003014.4 link	c.-256C>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000436072.7	NP_003005.2	Q6FHJ7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SFRP4	ENST00000436072.7 link	c.-256C>G	5_prime_UTR_variant	Exon 1 of 6	1	NM_003014.4	ENSP00000410715.2	Q6FHJ7
ENSG00000290149	ENST00000476620.1 link	c.-37-32047G>C	intron_variant	Intron 2 of 3	4		ENSP00000425858.1	D6RIH7
SFRP4	ENST00000447200.2 link	c.44-2340C>G	intron_variant	Intron 2 of 5	5		ENSP00000402262.2	C9JMJ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

422982

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

221668

African (AFR)

AF:

0.00

AC:

AN:

11548

American (AMR)

AF:

0.00

AC:

AN:

16826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12870

East Asian (EAS)

AF:

0.00

AC:

AN:

29002

South Asian (SAS)

AF:

0.00

AC:

AN:

41694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27774

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1864

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

256832

Other (OTH)

AF:

0.00

AC:

AN:

24572

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.0

(source)

DANN

Benign

0.87

PhyloP100

-0.48

PromoterAI

-0.017

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over