rs2740375

Variant names:

• chr11-618998-G-A
• rs2740375
• NM_021924.5:c.1561C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-618998-G-A
• chr11-618998-G-C
• chr11-618998-G-T

Variant summary

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

The NM_021924.5(CDHR5):​c.1561C>T​(p.Pro521Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,612,530 control chromosomes in the GnomAD database, including 242,696 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (18940 hom., cov: 29)
  • Exomes 𝑓: 0.55 (223756 hom.)
• Consequence: CDHR5 NM_021924.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.307
• Publications: 28 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.9095008E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR5	NM_021924.5	c.1561C>T	p.Pro521Ser	missense_variant	Exon 13 of 15	ENST00000397542.7	NP_068743.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR5	ENST00000397542.7	c.1561C>T	p.Pro521Ser	missense_variant	Exon 13 of 15	1	NM_021924.5	ENSP00000380676.2

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73107 AN: 150950 Hom.: 18946 Cov.: 29

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.491

GnomAD2 exomes AF: 0.542 AC: 135495 AN: 250138 AF XY: 0.551

Gnomad AFR exome AF: 0.286

Gnomad AMR exome AF: 0.416

Gnomad ASJ exome AF: 0.539

Gnomad EAS exome AF: 0.690

Gnomad FIN exome AF: 0.651

Gnomad NFE exome AF: 0.561

Gnomad OTH exome AF: 0.554

GnomAD4 exome AF: 0.550 AC: 803258 AN: 1461466 Hom.: 223756 Cov.: 71 AF XY: 0.552 AC XY: 401240 AN XY: 727052

African (AFR) AF: 0.281 AC: 9393 AN: 33466

American (AMR) AF: 0.421 AC: 18838 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 14075 AN: 26116

East Asian (EAS) AF: 0.731 AC: 29024 AN: 39698

South Asian (SAS) AF: 0.575 AC: 49629 AN: 86246

European-Finnish (FIN) AF: 0.637 AC: 33938 AN: 53278

Middle Eastern (MID) AF: 0.486 AC: 2800 AN: 5764

European-Non Finnish (NFE) AF: 0.551 AC: 612976 AN: 1111830

Other (OTH) AF: 0.540 AC: 32585 AN: 60374

GnomAD4 genome AF: 0.484 AC: 73111 AN: 151064 Hom.: 18940 Cov.: 29 AF XY: 0.491 AC XY: 36239 AN XY: 73764

African (AFR) AF: 0.290 AC: 11939 AN: 41184

American (AMR) AF: 0.446 AC: 6781 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1832 AN: 3468

East Asian (EAS) AF: 0.695 AC: 3505 AN: 5042

South Asian (SAS) AF: 0.589 AC: 2816 AN: 4778

European-Finnish (FIN) AF: 0.666 AC: 6991 AN: 10504

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37485 AN: 67570

Other (OTH) AF: 0.490 AC: 1030 AN: 2100

Alfa AF: 0.488 Hom.: 7381

Bravo AF: 0.461

TwinsUK AF: 0.543 AC: 2015

ALSPAC AF: 0.548 AC: 2113

ESP6500AA AF: 0.288 AC: 1270

ESP6500EA AF: 0.538 AC: 4629

ExAC AF: 0.543 AC: 65915

Asia WGS AF: 0.577 AC: 2008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.1
DANN	Benign	0.65
DEOGEN2	Benign	0.0053	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.34	T;.
MetaRNN	Benign	0.0000029	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L;L
PhyloP100		0.31
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.27	N;N
REVEL	Benign	0.0090
Sift	Benign	0.41	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.093	B;B
Vest4		0.19
MPC		0.057
ClinPred		0.0056	T
GERP RS		1.6
Varity_R		0.021
gMVP		0.29
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2740375; hg19: chr11-618998; COSMIC: COSV57641239; COSMIC: COSV57641239;