chr3-32289194-C-T

Position:

• chr3-32289194-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMTM8	NM_178868.5	c.147+50075C>T		intron_variant		ENST00000307526.4
CMTM8	NM_001320308.2	c.147+50075C>T		intron_variant
CMTM8	XM_011533416.4	c.216+6535C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CMTM8	ENST00000307526.4	c.147+50075C>T		intron_variant		1	NM_178868.5	P1
CMTM8	ENST00000458535.6	c.147+50075C>T		intron_variant		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

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.374

Alfa AF: 0.332 Hom.: 6613

Bravo AF: 0.380

Asia WGS AF: 0.229 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.44

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: rs4276227; hg19: chr3-32330686;