chr11-616865-G-A

Variant names:

• chr11-616865-G-A
• rs3758650
• NM_021924.5:c.*486C>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.*486C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 179,030 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.048 (256 hom., cov: 33)
  • Exomes 𝑓: 0.057 (65 hom.)
• Consequence: CDHR5 NM_021924.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693
• Publications: 25 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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR5	NM_021924.5	MANE Select	c.*486C>T		3_prime_UTR	Exon 15 of 15	NP_068743.3
	CDHR5	NM_001171968.3		c.*486C>T		3_prime_UTR	Exon 15 of 15	NP_001165439.2
	CDHR5	NM_031264.5		c.*486C>T		3_prime_UTR	Exon 14 of 14	NP_112554.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDHR5	ENST00000397542.7	TSL:1 MANE Select	c.*486C>T		3_prime_UTR	Exon 15 of 15	ENSP00000380676.2
	CDHR5	ENST00000358353.8	TSL:5	c.*486C>T		3_prime_UTR	Exon 15 of 15	ENSP00000351118.4

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7331 AN: 152166 Hom.: 258 Cov.: 33

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0271

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.0921

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0929

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.0396

GnomAD2 exomes AF: 0.0576 AC: 765 AN: 13282 AF XY: 0.0576

Gnomad AFR exome AF: 0.00718

Gnomad AMR exome AF: 0.0217

Gnomad ASJ exome AF: 0.0542

Gnomad EAS exome AF: 0.0824

Gnomad FIN exome AF: 0.0946

Gnomad NFE exome AF: 0.0548

Gnomad OTH exome AF: 0.0430

GnomAD4 exome AF: 0.0569 AC: 1522 AN: 26746 Hom.: 65 Cov.: 0 AF XY: 0.0607 AC XY: 885 AN XY: 14574

African (AFR) AF: 0.0213 AC: 7 AN: 328

American (AMR) AF: 0.0151 AC: 18 AN: 1192

Ashkenazi Jewish (ASJ) AF: 0.0402 AC: 23 AN: 572

East Asian (EAS) AF: 0.0717 AC: 42 AN: 586

South Asian (SAS) AF: 0.0883 AC: 399 AN: 4518

European-Finnish (FIN) AF: 0.0811 AC: 115 AN: 1418

Middle Eastern (MID) AF: 0.0419 AC: 72 AN: 1720

European-Non Finnish (NFE) AF: 0.0514 AC: 763 AN: 14856

Other (OTH) AF: 0.0533 AC: 83 AN: 1556

GnomAD4 genome AF: 0.0481 AC: 7328 AN: 152284 Hom.: 256 Cov.: 33 AF XY: 0.0512 AC XY: 3814 AN XY: 74452

African (AFR) AF: 0.0171 AC: 710 AN: 41580

American (AMR) AF: 0.0269 AC: 412 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 147 AN: 3472

East Asian (EAS) AF: 0.0923 AC: 477 AN: 5168

South Asian (SAS) AF: 0.111 AC: 538 AN: 4834

European-Finnish (FIN) AF: 0.0929 AC: 985 AN: 10606

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0572 AC: 3889 AN: 67996

Other (OTH) AF: 0.0388 AC: 82 AN: 2116

Alfa AF: 0.0506 Hom.: 489

Bravo AF: 0.0404

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.77
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3758650; hg19: chr11-616865; COSMIC: COSV52759201; COSMIC: COSV52759201;