rs36015759

Variant names:

• chr11-119345569-G-A
• rs36015759
• NM_031433.4:c.492C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-119345569-G-A
• chr11-119345569-G-C
• chr11-119345569-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_031433.4(MFRP):​c.492C>T​(p.Tyr164Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,692 control chromosomes in the GnomAD database, including 37,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3717 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33970 hom.)
• Consequence: MFRP NM_031433.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.39
• Publications: 24 publications found

Genes affected

MFRP (HGNC:18121): (membrane frizzled-related protein) This gene encodes a member of the frizzled-related protein family. The encoded protein plays an important role in eye development and mutations in this gene have been associated with nanophthalmos, posterior microphthalmia, retinitis pigmentosa, foveoschisis, and optic disc drusen. The protein is encoded by a bicistronic transcript which also encodes C1q and tumor necrosis factor related protein 5 (C1QTNF5). [provided by RefSeq, Jun 2013]

C1QTNF5 (HGNC:14344): (C1q and TNF related 5) This gene encodes a member of a family of proteins that function as components of basement membranes and may play a role in cell adhesion. Mutations in this gene have been associated with late-onset retinal degeneration. The protein may be encoded by either a bicistronic transcript including sequence from the upstream membrane frizzled-related protein gene (MFRP), or by a monocistronic transcript expressed from an internal promoter. [provided by RefSeq, Jun 2013]

C1QTNF5 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• late-onset retinal degeneration

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 11-119345569-G-A is Benign according to our data. Variant chr11-119345569-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 143157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031433.4. 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
	MFRP	NM_031433.4	MANE Select	c.492C>T	p.Tyr164Tyr	synonymous	Exon 5 of 15	NP_113621.1	Q9BY79-1
	C1QTNF5	NM_015645.5		c.-2145C>T		5_prime_UTR	Exon 5 of 15	NP_056460.1	Q9BXJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFRP	ENST00000619721.6	TSL:1 MANE Select	c.492C>T	p.Tyr164Tyr	synonymous	Exon 5 of 15	ENSP00000481824.1	Q9BY79-1
	MFRP	ENST00000360167.4	TSL:2	c.492C>T	p.Tyr164Tyr	synonymous	Exon 5 of 10	ENSP00000353291.4	Q9BY79-2
	MFRP	ENST00000529147.2	TSL:5	n.455C>T		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33077 AN: 151996 Hom.: 3714 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.208 AC: 51693 AN: 248354 AF XY: 0.207

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.272

Gnomad EAS exome AF: 0.219

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.213 AC: 311105 AN: 1461578 Hom.: 33970 Cov.: 60 AF XY: 0.211 AC XY: 153463 AN XY: 727098

African (AFR) AF: 0.233 AC: 7808 AN: 33478

American (AMR) AF: 0.118 AC: 5273 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6968 AN: 26134

East Asian (EAS) AF: 0.179 AC: 7118 AN: 39700

South Asian (SAS) AF: 0.160 AC: 13841 AN: 86256

European-Finnish (FIN) AF: 0.297 AC: 15794 AN: 53220

Middle Eastern (MID) AF: 0.128 AC: 736 AN: 5768

European-Non Finnish (NFE) AF: 0.217 AC: 241302 AN: 1111916

Other (OTH) AF: 0.203 AC: 12265 AN: 60390

GnomAD4 genome AF: 0.218 AC: 33088 AN: 152114 Hom.: 3717 Cov.: 32 AF XY: 0.216 AC XY: 16084 AN XY: 74372

African (AFR) AF: 0.228 AC: 9474 AN: 41492

American (AMR) AF: 0.151 AC: 2312 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1013 AN: 5150

South Asian (SAS) AF: 0.159 AC: 766 AN: 4826

European-Finnish (FIN) AF: 0.287 AC: 3037 AN: 10592

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14941 AN: 67978

Other (OTH) AF: 0.193 AC: 407 AN: 2112

Alfa AF: 0.204 Hom.: 5708

Bravo AF: 0.210

Asia WGS AF: 0.169 AC: 591 AN: 3478

EpiCase AF: 0.205

EpiControl AF: 0.204

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Isolated microphthalmia 5 (1)
-	-	1	Isolated microphthalmia 6 (1)
-	-	1	Retinal degeneration (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.4
DANN	Benign	0.93
PhyloP100		1.4
Mutation Taster		=292/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs36015759; hg19: chr11-119216279; COSMIC: COSV64127956; COSMIC: COSV64127956;