chr1-159177662-C-T

Variant names:

• chr1-159177662-C-T
• rs3026968
• NM_001127173.3:c.88+5809C>T

Variant summary

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

The NM_001127173.3(CADM3):​c.88+5809C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,038 control chromosomes in the GnomAD database, including 4,527 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 0.21 (4527 hom., cov: 32)
• Consequence: CADM3 NM_001127173.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890

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]

AIM2 (HGNC:357): (absent in melanoma 2) AIM2 is a member of the IFI20X /IFI16 family. It plays a putative role in tumorigenic reversion and may control cell proliferation. Interferon-gamma induces expression of AIM2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM3	NM_001127173.3	c.88+5809C>T		intron_variant	Intron 1 of 8	ENST00000368125.9	NP_001120645.1
CADM3	NM_021189.5	c.88+5809C>T		intron_variant	Intron 1 of 9		NP_067012.1
CADM3	NM_001346510.2	c.88+5809C>T		intron_variant	Intron 1 of 8		NP_001333439.1
CADM3	XM_024448760.2	c.88+5809C>T		intron_variant	Intron 1 of 11		XP_024304528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM3	ENST00000368125.9	c.88+5809C>T		intron_variant	Intron 1 of 8	1	NM_001127173.3	ENSP00000357107.4
CADM3	ENST00000368124.8	c.88+5809C>T		intron_variant	Intron 1 of 9	1		ENSP00000357106.4
CADM3	ENST00000416746.1	c.88+5809C>T		intron_variant	Intron 1 of 6	1		ENSP00000387802.1
AIM2	ENST00000695582.1	n.33+10149G>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31927 AN: 151920 Hom.: 4517 Cov.: 32

Gnomad AFR AF: 0.0532

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 31939 AN: 152038 Hom.: 4527 Cov.: 32 AF XY: 0.221 AC XY: 16451 AN XY: 74324

Gnomad4 AFR AF: 0.0531

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.222

Alfa AF: 0.230 Hom.: 6620

Bravo AF: 0.206

Asia WGS AF: 0.392 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.49

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: rs3026968; hg19: chr1-159147452;