3-32281483-A-T

Variant names:

• chr3-32281483-A-T
• rs6783478
• NM_178868.5:c.147+42364A>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.147+42364A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,934 control chromosomes in the GnomAD database, including 16,972 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 0.47 (16972 hom., cov: 31)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178868.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTM8	NM_178868.5	MANE Select	c.147+42364A>T		intron	N/A	NP_849199.2
	CMTM8	NM_001320308.2		c.147+42364A>T		intron	N/A	NP_001307237.1	Q8IZV2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTM8	ENST00000307526.4	TSL:1 MANE Select	c.147+42364A>T		intron	N/A	ENSP00000307741.3	Q8IZV2-1
	CMTM8	ENST00000458535.6	TSL:1	c.147+42364A>T		intron	N/A	ENSP00000412934.2	Q8IZV2-2
	CMTM8	ENST00000867234.1		c.148-29057A>T		intron	N/A	ENSP00000537293.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71692 AN: 151816 Hom.: 16966 Cov.: 31

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.472 AC: 71740 AN: 151934 Hom.: 16972 Cov.: 31 AF XY: 0.473 AC XY: 35101 AN XY: 74234

African (AFR) AF: 0.437 AC: 18101 AN: 41424

American (AMR) AF: 0.465 AC: 7094 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1879 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2256 AN: 5144

South Asian (SAS) AF: 0.548 AC: 2633 AN: 4806

European-Finnish (FIN) AF: 0.436 AC: 4606 AN: 10558

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.493 AC: 33512 AN: 67958

Other (OTH) AF: 0.470 AC: 993 AN: 2112

Alfa AF: 0.472 Hom.: 2048

Bravo AF: 0.469

Asia WGS AF: 0.506 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.58
PhyloP100		-0.27
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: rs6783478; hg19: chr3-32322975;