chr11-618013-C-T

Position:

• chr11-618013-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021924.5(CDHR5):​c.2059G>A​(p.Ala687Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,610,710 control chromosomes in the GnomAD database, including 39,855 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 0.22 (3906 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35949 hom.)
• Consequence: CDHR5 NM_021924.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004850924).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR5	NM_021924.5	c.2059G>A	p.Ala687Thr	missense_variant	14/15	ENST00000397542.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR5	ENST00000397542.7	c.2059G>A	p.Ala687Thr	missense_variant	14/15	1	NM_021924.5	P2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33697 AN: 151892 Hom.: 3906 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.0967

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.233

GnomAD3 exomes AF: 0.196 AC: 48179 AN: 245240 Hom.: 5343 AF XY: 0.189 AC XY: 25208 AN XY: 133380

Gnomad AFR exome AF: 0.266

Gnomad AMR exome AF: 0.281

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.0277

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.216 AC: 314968 AN: 1458700 Hom.: 35949 Cov.: 38 AF XY: 0.212 AC XY: 153841 AN XY: 725696

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.0226

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.222 AC: 33717 AN: 152010 Hom.: 3906 Cov.: 32 AF XY: 0.213 AC XY: 15846 AN XY: 74304

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0250

Gnomad4 SAS AF: 0.0957

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.232

Alfa AF: 0.231 Hom.: 2056

Bravo AF: 0.232

TwinsUK AF: 0.225 AC: 834

ALSPAC AF: 0.238 AC: 916

ESP6500AA AF: 0.275 AC: 1212

ESP6500EA AF: 0.242 AC: 2084

ExAC AF: 0.194 AC: 23436

Asia WGS AF: 0.0900 AC: 313 AN: 3478

EpiCase AF: 0.233

EpiControl AF: 0.228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.93
DANN	Benign	0.71
DEOGEN2	Benign	0.0088	T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.51	T;.;T
MetaRNN	Benign	0.0049	T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.65	N;N;N
REVEL	Benign	0.0070
Sift	Benign	0.45	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0050	B;B;B
Vest4		0.11
MPC		0.042
ClinPred		0.00082	T
GERP RS		-3.3
Varity_R		0.021
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs7108757; hg19: chr11-618013; COSMIC: COSV57641516; COSMIC: COSV57641516;