7-37907482-C-G

Variant names:

• chr7-37907482-C-G
• rs35937440
• NM_003014.4:c.1038G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003014.4(SFRP4):​c.1038G>C​(p.Val346Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000786 in 1,612,320 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00045 (2 hom.)
• Consequence: SFRP4 NM_003014.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0260
• Publications: 1 publications found

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: Orphanet, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000290149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-37907482-C-G is Benign according to our data. Variant chr7-37907482-C-G is described in ClinVar as Benign. ClinVar VariationId is 788420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.026 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00401 (611/152328) while in subpopulation AFR AF = 0.014 (580/41574). AF 95% confidence interval is 0.013. There are 3 homozygotes in GnomAd4. There are 271 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003014.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP4	NM_003014.4	MANE Select	c.1038G>C	p.Val346Val	synonymous	Exon 6 of 6	NP_003005.2	Q6FHJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP4	ENST00000436072.7	TSL:1 MANE Select	c.1038G>C	p.Val346Val	synonymous	Exon 6 of 6	ENSP00000410715.2	Q6FHJ7
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-37-41358C>G		intron	N/A	ENSP00000425858.1	D6RIH7
	SFRP4	ENST00000960684.1		c.1062G>C	p.Val354Val	synonymous	Exon 6 of 6	ENSP00000630743.1

Frequencies

GnomAD3 genomes AF: 0.00399 AC: 607 AN: 152210 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

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: 0.000103

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00107 AC: 267 AN: 249900 AF XY: 0.000822

Gnomad AFR exome AF: 0.0141

Gnomad AMR exome AF: 0.000612

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000823

GnomAD4 exome AF: 0.000450 AC: 657 AN: 1459992 Hom.: 2 Cov.: 29 AF XY: 0.000409 AC XY: 297 AN XY: 726342

African (AFR) AF: 0.0142 AC: 473 AN: 33252

American (AMR) AF: 0.000877 AC: 39 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 86002

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53378

Middle Eastern (MID) AF: 0.00210 AC: 12 AN: 5720

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111250

Other (OTH) AF: 0.00121 AC: 73 AN: 60272

GnomAD4 genome AF: 0.00401 AC: 611 AN: 152328 Hom.: 3 Cov.: 33 AF XY: 0.00364 AC XY: 271 AN XY: 74490

African (AFR) AF: 0.0140 AC: 580 AN: 41574

American (AMR) AF: 0.00111 AC: 17 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68028

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00125 Hom.: 1

Bravo AF: 0.00419

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.51
DANN	Benign	0.60
PhyloP100		-0.026
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs35937440; hg19: chr7-37947084;