rs862991

chr1-159194574-G-A

Variant summary

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

The NM_001127173.3(CADM3):c.691+534G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,340 control chromosomes in the GnomAD database, including 35,254 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 0.67 (35216 hom., cov: 33)
  • Exomes 𝑓: 0.66 (38 hom.)
• Consequence: CADM3 NM_001127173.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

Genes affected

CADM3 (HGNC:17601): (cell adhesion molecule 3) The protein encoded by this gene is a calcium-independent cell-cell adhesion protein that can form homodimers or heterodimers with other nectin proteins. The encoded protein has both homophilic and heterophilic cell-cell adhesion activity. This gene is reported to be a tumor suppressor gene. [provided by RefSeq, Oct 2016]

CADM3-AS1 (HGNC:40812): (CADM3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM3	NM_001127173.3	c.691+534G>A		intron_variant		ENST00000368125.9
CADM3	NM_001346510.2	c.553+672G>A		intron_variant
CADM3	NM_021189.5	c.793+534G>A		intron_variant
CADM3	XM_024448760.2	c.940+534G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM3	ENST00000368125.9	c.691+534G>A		intron_variant		1	NM_001127173.3	P2
CADM3	ENST00000368124.8	c.793+534G>A		intron_variant		1		A2
CADM3	ENST00000416746.1	c.553+672G>A		intron_variant		1
CADM3-AS1	ENST00000415675.3	n.4795C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102124 AN: 152046 Hom.: 35207 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.692

GnomAD4 exome AF: 0.665 AC: 117 AN: 176 Hom.: 38 Cov.: 0 AF XY: 0.688 AC XY: 55 AN XY: 80

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.667

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.662

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.671 AC: 102164 AN: 152164 Hom.: 35216 Cov.: 33 AF XY: 0.672 AC XY: 50014 AN XY: 74396

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.745

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.695

Alfa AF: 0.711 Hom.: 44492

Bravo AF: 0.665

Asia WGS AF: 0.796 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.17
Dann	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs862991; hg19: chr1-159164364;