rs756764471

Variant names:

• chr11-617656-C-A
• rs756764471
• NM_021924.5:c.2233G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-617656-C-A
• chr11-617656-C-G
• chr11-617656-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021924.5(CDHR5):​c.2233G>T​(p.Ala745Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,526,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A745T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CDHR5 NM_021924.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 2 publications found

Genes affected

CDHR5 (HGNC:7521): (cadherin related family member 5) This gene is a novel mucin-like gene that is a member of the cadherin superfamily. While encoding nonpolymorphic tandem repeats rich in proline, serine and threonine similar to mucin proteins, the gene also contains sequence encoding calcium-binding motifs found in all cadherins. The role of the hybrid extracellular region and the specific function of this protein have not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041347384).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021924.5. 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
	CDHR5	NM_021924.5	MANE Select	c.2233G>T	p.Ala745Ser	missense	Exon 15 of 15	NP_068743.3	Q9HBB8-1
	CDHR5	NM_001171968.3		c.2215G>T	p.Ala739Ser	missense	Exon 15 of 15	NP_001165439.2	Q9HBB8-4
	CDHR5	NM_031264.5		c.1651G>T	p.Ala551Ser	missense	Exon 14 of 14	NP_112554.3	Q9HBB8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR5	ENST00000397542.7	TSL:1 MANE Select	c.2233G>T	p.Ala745Ser	missense	Exon 15 of 15	ENSP00000380676.2	Q9HBB8-1
	CDHR5	ENST00000349570.11	TSL:1	c.1651G>T	p.Ala551Ser	missense	Exon 14 of 14	ENSP00000345726.7	Q9HBB8-2
	CDHR5	ENST00000872876.1		c.2317G>T	p.Ala773Ser	missense	Exon 16 of 16	ENSP00000542935.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152110 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1374014 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 677378

African (AFR) AF: 0.00 AC: 0 AN: 30634

American (AMR) AF: 0.00 AC: 0 AN: 31406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22836

East Asian (EAS) AF: 0.00 AC: 0 AN: 36338

South Asian (SAS) AF: 0.00 AC: 0 AN: 76496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5166

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1072712

Other (OTH) AF: 0.00 AC: 0 AN: 56982

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152110 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74300

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.1
DANN	Benign	0.85
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.012
Sift	Benign	0.36	T
Sift4G	Benign	0.52	T
Polyphen		0.070	B
Vest4		0.041
MutPred		0.17		Gain of glycosylation at A745 (P = 0.0018)
MVP		0.048
MPC		0.087
ClinPred		0.13	T
GERP RS		-0.40
Varity_R		0.038
gMVP		0.16
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs756764471; hg19: chr11-617656;