3-32285929-A-G

Position:

• chr3-32285929-A-G

Variant summary

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

The NM_178868.5(CMTM8):​c.147+46810A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 152,062 control chromosomes in the GnomAD database, including 17,839 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 0.48 (17839 hom., cov: 33)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMTM8	NM_178868.5	c.147+46810A>G		intron_variant		ENST00000307526.4
CMTM8	NM_001320308.2	c.147+46810A>G		intron_variant
CMTM8	XM_011533416.4	c.216+3270A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMTM8	ENST00000307526.4	c.147+46810A>G		intron_variant		1	NM_178868.5	P1
CMTM8	ENST00000458535.6	c.147+46810A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72934 AN: 151944 Hom.: 17842 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.480 AC: 72950 AN: 152062 Hom.: 17839 Cov.: 33 AF XY: 0.479 AC XY: 35623 AN XY: 74332

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.488

Alfa AF: 0.491 Hom.: 3182

Bravo AF: 0.475

Asia WGS AF: 0.505 AC: 1757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.90
DANN	Benign	0.56

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: rs4955274; hg19: chr3-32327421;