7-37907562-G-T

Position:

• chr7-37907562-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003014.4(SFRP4):​c.958C>A​(p.Pro320Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,612,272 control chromosomes in the GnomAD database, including 135,524 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.46 (16582 hom., cov: 32)
  • Exomes 𝑓: 0.40 (118942 hom.)
• Consequence: SFRP4 NM_003014.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.432

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]

ENSG00000290149 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.5010467E-5).
• BP6: Variant 7-37907562-G-T is Benign according to our data. Variant chr7-37907562-G-T is described in ClinVar as [Benign]. Clinvar id is 1287094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFRP4	NM_003014.4	c.958C>A	p.Pro320Thr	missense_variant	6/6	ENST00000436072.7	NP_003005.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFRP4	ENST00000436072.7	c.958C>A	p.Pro320Thr	missense_variant	6/6	1	NM_003014.4	ENSP00000410715.2
ENSG00000290149	ENST00000476620.1	c.-37-41278G>T		intron_variant		4		ENSP00000425858.1
SFRP4	ENST00000478975.1	n.326C>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69168 AN: 151686 Hom.: 16558 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.455

GnomAD3 exomes AF: 0.437 AC: 109702 AN: 251174 Hom.: 24781 AF XY: 0.435 AC XY: 59036 AN XY: 135740

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.465

Gnomad ASJ exome AF: 0.423

Gnomad EAS exome AF: 0.553

Gnomad SAS exome AF: 0.524

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.375

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.400 AC: 583939 AN: 1460468 Hom.: 118942 Cov.: 35 AF XY: 0.403 AC XY: 292492 AN XY: 726542

Gnomad4 AFR exome AF: 0.579

Gnomad4 AMR exome AF: 0.466

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.522

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.456 AC: 69240 AN: 151804 Hom.: 16582 Cov.: 32 AF XY: 0.460 AC XY: 34099 AN XY: 74178

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.457

Alfa AF: 0.381 Hom.: 15864

Bravo AF: 0.463

TwinsUK AF: 0.382 AC: 1416

ALSPAC AF: 0.390 AC: 1504

ESP6500AA AF: 0.568 AC: 2501

ESP6500EA AF: 0.361 AC: 3106

ExAC AF: 0.438 AC: 53190

Asia WGS AF: 0.518 AC: 1803 AN: 3478

EpiCase AF: 0.383

EpiControl AF: 0.383

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 25, 2021	This variant is associated with the following publications: (PMID: 26715268) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Pyle metaphyseal dysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

SFRP4-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.000045	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.071
Sift	Benign	0.17	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.036
MPC		0.42
ClinPred		0.0055	T
GERP RS		3.0
Varity_R		0.046
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs1802073; hg19: chr7-37947164; COSMIC: COSV71412319; COSMIC: COSV71412319;