rs1370717

chr3-32312895-G-Achr3-32312895-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.148-44478G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,418 control chromosomes in the GnomAD database, including 12,962 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 0.39 (12962 hom., cov: 29)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMTM8	NM_178868.5	c.148-44478G>A		intron_variant		ENST00000307526.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMTM8	ENST00000307526.4	c.148-44478G>A		intron_variant		1	NM_178868.5	P1
CMTM8	ENST00000458535.6	c.148-54977G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59676 AN: 151300 Hom.: 12962 Cov.: 29

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.394 AC: 59697 AN: 151418 Hom.: 12962 Cov.: 29 AF XY: 0.400 AC XY: 29595 AN XY: 73972

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.420

Alfa AF: 0.435 Hom.: 15340

Bravo AF: 0.398

Asia WGS AF: 0.562 AC: 1953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.87
Dann	Benign	0.43

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: rs1370717; hg19: chr3-32354387;