rs71546610

Variant names:

• chr7-37916793-G-A
• rs71546610
• NM_003014.4:c.-256C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-37916793-G-A
• chr7-37916793-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003014.4(SFRP4):​c.-256C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 574,606 control chromosomes in the GnomAD database, including 18,657 homozygotes. 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: 𝑓 0.27 (5570 hom., cov: 33)
  • Exomes 𝑓: 0.25 (13087 hom.)
• Consequence: SFRP4 NM_003014.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477
• Publications: 6 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000290149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40780 AN: 152072 Hom.: 5558 Cov.: 33

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.245 AC: 103580 AN: 422416 Hom.: 13087 Cov.: 4 AF XY: 0.245 AC XY: 54151 AN XY: 221362

African (AFR) AF: 0.347 AC: 4002 AN: 11532

American (AMR) AF: 0.277 AC: 4658 AN: 16814

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 3488 AN: 12846

East Asian (EAS) AF: 0.218 AC: 6318 AN: 28970

South Asian (SAS) AF: 0.236 AC: 9836 AN: 41648

European-Finnish (FIN) AF: 0.216 AC: 5988 AN: 27736

Middle Eastern (MID) AF: 0.266 AC: 495 AN: 1860

European-Non Finnish (NFE) AF: 0.244 AC: 62678 AN: 256478

Other (OTH) AF: 0.249 AC: 6117 AN: 24532

GnomAD4 genome AF: 0.268 AC: 40833 AN: 152190 Hom.: 5570 Cov.: 33 AF XY: 0.266 AC XY: 19769 AN XY: 74412

African (AFR) AF: 0.341 AC: 14141 AN: 41530

American (AMR) AF: 0.259 AC: 3958 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 949 AN: 3472

East Asian (EAS) AF: 0.219 AC: 1128 AN: 5162

South Asian (SAS) AF: 0.234 AC: 1130 AN: 4822

European-Finnish (FIN) AF: 0.215 AC: 2283 AN: 10598

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16436 AN: 67992

Other (OTH) AF: 0.255 AC: 537 AN: 2108

Alfa AF: 0.260 Hom.: 688

Bravo AF: 0.279

Asia WGS AF: 0.238 AC: 826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.1
DANN	Benign	0.92
PhyloP100		-0.48
PromoterAI		0.023	Neutral
Mutation Taster		=295/5	polymorphism (auto)

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: rs71546610; hg19: chr7-37956395; COSMIC: COSV52260123; COSMIC: COSV52260123;