11-618013-C-T

Variant names:

• chr11-618013-C-T
• rs7108757
• NM_021924.5:c.2059G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/20 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
• Publications: 16 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=0.004850924).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

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.2059G>A	p.Ala687Thr	missense	Exon 14 of 15	NP_068743.3	Q9HBB8-1
	CDHR5	NM_001171968.3		c.2041G>A	p.Ala681Thr	missense	Exon 14 of 15	NP_001165439.2	Q9HBB8-4
	CDHR5	NM_031264.5		c.1477G>A	p.Ala493Thr	missense	Exon 13 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.2059G>A	p.Ala687Thr	missense	Exon 14 of 15	ENSP00000380676.2	Q9HBB8-1
	CDHR5	ENST00000349570.11	TSL:1	c.1477G>A	p.Ala493Thr	missense	Exon 13 of 14	ENSP00000345726.7	Q9HBB8-2
	CDHR5	ENST00000872876.1		c.2143G>A	p.Ala715Thr	missense	Exon 15 of 16	ENSP00000542935.1

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

GnomAD2 exomes AF: 0.196 AC: 48179 AN: 245240 AF XY: 0.189

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 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

African (AFR) AF: 0.268 AC: 8972 AN: 33446

American (AMR) AF: 0.278 AC: 12358 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5821 AN: 26096

East Asian (EAS) AF: 0.0226 AC: 897 AN: 39684

South Asian (SAS) AF: 0.107 AC: 9215 AN: 86110

European-Finnish (FIN) AF: 0.155 AC: 8029 AN: 51934

Middle Eastern (MID) AF: 0.165 AC: 951 AN: 5768

European-Non Finnish (NFE) AF: 0.231 AC: 256258 AN: 1110842

Other (OTH) AF: 0.207 AC: 12467 AN: 60320

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

African (AFR) AF: 0.267 AC: 11048 AN: 41438

American (AMR) AF: 0.245 AC: 3753 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 799 AN: 3466

East Asian (EAS) AF: 0.0250 AC: 129 AN: 5168

South Asian (SAS) AF: 0.0957 AC: 461 AN: 4816

European-Finnish (FIN) AF: 0.144 AC: 1521 AN: 10586

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15304 AN: 67940

Other (OTH) AF: 0.232 AC: 487 AN: 2102

Alfa AF: 0.226 Hom.: 2654

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 v4.9

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
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.98	T
PhyloP100		-1.0
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.0070
Sift	Benign	0.45	T
Sift4G	Benign	0.52	T
Polyphen		0.0050	B
Vest4		0.11
MPC		0.042
ClinPred		0.00082	T
GERP RS		-3.3
Varity_R		0.021
gMVP		0.15
Mutation Taster		=100/0	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: rs7108757; hg19: chr11-618013; COSMIC: COSV57641516; COSMIC: COSV57641516;