3-32289194-C-T

Variant names:

• chr3-32289194-C-T
• rs4276227
• NM_178868.5:c.147+50075C>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+50075C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,026 control chromosomes in the GnomAD database, including 10,190 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 0.36 (10190 hom., cov: 32)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 6 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.476 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+50075C>T		intron	N/A	NP_849199.2
	CMTM8	NM_001320308.2		c.147+50075C>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+50075C>T		intron	N/A	ENSP00000307741.3	Q8IZV2-1
	CMTM8	ENST00000458535.6	TSL:1	c.147+50075C>T		intron	N/A	ENSP00000412934.2	Q8IZV2-2
	CMTM8	ENST00000867234.1		c.148-21346C>T		intron	N/A	ENSP00000537293.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54351 AN: 151908 Hom.: 10182 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.358 AC: 54399 AN: 152026 Hom.: 10190 Cov.: 32 AF XY: 0.353 AC XY: 26247 AN XY: 74332

African (AFR) AF: 0.417 AC: 17292 AN: 41438

American (AMR) AF: 0.485 AC: 7411 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3468

East Asian (EAS) AF: 0.136 AC: 703 AN: 5184

South Asian (SAS) AF: 0.222 AC: 1067 AN: 4816

European-Finnish (FIN) AF: 0.261 AC: 2765 AN: 10580

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22978 AN: 67958

Other (OTH) AF: 0.374 AC: 788 AN: 2108

Alfa AF: 0.337 Hom.: 9429

Bravo AF: 0.380

Asia WGS AF: 0.229 AC: 793 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	2.1
DANN	Benign	0.44
PhyloP100		0.052
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: rs4276227; hg19: chr3-32330686;