1-159178723-C-T

Position:

• chr1-159178723-C-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+6870C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 151,942 control chromosomes in the GnomAD database, including 32,085 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 0.65 (32085 hom., cov: 31)
• Consequence: CADM3 NM_001127173.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM3	NM_001127173.3	c.88+6870C>T		intron_variant		ENST00000368125.9
CADM3	NM_001346510.2	c.88+6870C>T		intron_variant
CADM3	NM_021189.5	c.88+6870C>T		intron_variant
CADM3	XM_024448760.2	c.88+6870C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM3	ENST00000368125.9	c.88+6870C>T		intron_variant		1	NM_001127173.3	P2
CADM3	ENST00000368124.8	c.88+6870C>T		intron_variant		1		A2
CADM3	ENST00000416746.1	c.88+6870C>T		intron_variant		1
AIM2	ENST00000695582.1	n.33+9088G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98290 AN: 151824 Hom.: 32059 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.647 AC: 98362 AN: 151942 Hom.: 32085 Cov.: 31 AF XY: 0.651 AC XY: 48323 AN XY: 74232

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.654

Alfa AF: 0.607 Hom.: 58134

Bravo AF: 0.658

Asia WGS AF: 0.588 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.57

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: rs1474747; hg19: chr1-159148513;