4-153788590-C-T

Variant names:

• chr4-153788590-C-T
• rs79844222
• NM_003013.3:c.246G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_003013.3(SFRP2):​c.246G>A​(p.Leu82Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,614,162 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (17 hom., cov: 33)
  • Exomes 𝑓: 0.00082 (15 hom.)
• Consequence: SFRP2 NM_003013.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.239
• Publications: 1 publications found

Genes affected

SFRP2 (HGNC:10777): (secreted frizzled related protein 2) This gene encodes 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. Methylation of this gene is a potential marker for the presence of colorectal cancer. [provided by RefSeq, Jul 2008]

ENSG00000280241 (HGNC:58900):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 4-153788590-C-T is Benign according to our data. Variant chr4-153788590-C-T is described in ClinVar as Benign. ClinVar VariationId is 776025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.239 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00827 (1259/152290) while in subpopulation AFR AF = 0.0286 (1189/41574). AF 95% confidence interval is 0.0272. There are 17 homozygotes in GnomAd4. There are 593 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1259 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003013.3. 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
	SFRP2	NM_003013.3	MANE Select	c.246G>A	p.Leu82Leu	synonymous	Exon 1 of 3	NP_003004.1	A0A140VJU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP2	ENST00000274063.5	TSL:1 MANE Select	c.246G>A	p.Leu82Leu	synonymous	Exon 1 of 3	ENSP00000274063.4	Q96HF1
	SFRP2	ENST00000918154.1		c.246G>A	p.Leu82Leu	synonymous	Exon 1 of 3	ENSP00000588213.1
	ENSG00000280241	ENST00000839747.1		n.99+29024C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00825 AC: 1256 AN: 152172 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

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: 0.000118

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00208 AC: 524 AN: 251362 AF XY: 0.00152

Gnomad AFR exome AF: 0.0285

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000825 AC: 1206 AN: 1461872 Hom.: 15 Cov.: 74 AF XY: 0.000712 AC XY: 518 AN XY: 727234

African (AFR) AF: 0.0289 AC: 966 AN: 33480

American (AMR) AF: 0.00141 AC: 63 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1111996

Other (OTH) AF: 0.00194 AC: 117 AN: 60396

GnomAD4 genome AF: 0.00827 AC: 1259 AN: 152290 Hom.: 17 Cov.: 33 AF XY: 0.00796 AC XY: 593 AN XY: 74478

African (AFR) AF: 0.0286 AC: 1189 AN: 41574

American (AMR) AF: 0.00301 AC: 46 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68012

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

Alfa AF: 0.00285 Hom.: 7

Bravo AF: 0.00948

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.5
DANN	Benign	0.91
PhyloP100		0.24
PromoterAI		-0.064	Neutral
Mutation Taster		=94/6	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: rs79844222; hg19: chr4-154709742;