rs12496256

chr3-32258057-G-Achr3-32258057-G-T

Variant summary

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

The NM_178868.5(CMTM8):c.147+18938G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 151,838 control chromosomes in the GnomAD database, including 34,454 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 (34454 hom., cov: 30)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

Genes affected

CMTM8 (HGNC:19179): (CKLF like MARVEL transmembrane domain containing 8) This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and the transmembrane 4 superfamilies. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 3. This gene acts as a tumor suppressor, and plays a role in regulating the migration of tumor cells. The encoded protein is thought to function as a a negative regulator of epidermal growth factor-induced signaling. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMTM8	NM_178868.5	c.147+18938G>A		intron_variant		ENST00000307526.4
CMTM8	NM_001320308.2	c.147+18938G>A		intron_variant
CMTM8	XM_011533416.4	c.147+18938G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMTM8	ENST00000307526.4	c.147+18938G>A		intron_variant		1	NM_178868.5	P1
CMTM8	ENST00000458535.6	c.147+18938G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.672 AC: 101978 AN: 151718 Hom.: 34440 Cov.: 30

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.672 AC: 102035 AN: 151838 Hom.: 34454 Cov.: 30 AF XY: 0.669 AC XY: 49618 AN XY: 74188

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.678

Alfa AF: 0.662 Hom.: 42040

Bravo AF: 0.679

Asia WGS AF: 0.533 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.3
Dann	Benign	0.93

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: rs12496256; hg19: chr3-32299549;