3-32324296-C-T

Variant names:

• chr3-32324296-C-T
• rs1438182
• NM_178868.5:c.148-33077C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178868.5(CMTM8):​c.148-33077C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 152,150 control chromosomes in the GnomAD database, including 483 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 0.077 (483 hom., cov: 32)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMTM8	NM_178868.5	c.148-33077C>T		intron_variant	Intron 1 of 3	ENST00000307526.4	NP_849199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMTM8	ENST00000307526.4	c.148-33077C>T		intron_variant	Intron 1 of 3	1	NM_178868.5	ENSP00000307741.3
CMTM8	ENST00000458535.6	c.148-43576C>T		intron_variant	Intron 1 of 2	1		ENSP00000412934.2

Frequencies

GnomAD3 genomes AF: 0.0771 AC: 11722 AN: 152034 Hom.: 483 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.0790

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

GnomAD4 genome AF: 0.0770 AC: 11723 AN: 152150 Hom.: 483 Cov.: 32 AF XY: 0.0745 AC XY: 5542 AN XY: 74388

African (AFR) AF: 0.0412 AC: 1709 AN: 41508

American (AMR) AF: 0.0723 AC: 1104 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 469 AN: 3462

East Asian (EAS) AF: 0.0503 AC: 261 AN: 5184

South Asian (SAS) AF: 0.0914 AC: 441 AN: 4826

European-Finnish (FIN) AF: 0.0662 AC: 700 AN: 10576

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0986 AC: 6706 AN: 68006

Other (OTH) AF: 0.0791 AC: 167 AN: 2110

Alfa AF: 0.0905 Hom.: 1236

Bravo AF: 0.0737

Asia WGS AF: 0.0770 AC: 265 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	2.6
DANN	Benign	0.70
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1438182; hg19: chr3-32365788;