rs9833771

Positions:

• chr3-32321506-T-C

Variant summary

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

The NM_178868.5(CMTM8):​c.148-35867T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,936 control chromosomes in the GnomAD database, including 11,459 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 0.38 (11459 hom., cov: 31)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM8	NM_178868.5	c.148-35867T>C		intron_variant		ENST00000307526.4	NP_849199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTM8	ENST00000307526.4	c.148-35867T>C		intron_variant		1	NM_178868.5	ENSP00000307741.3
CMTM8	ENST00000458535.6	c.148-46366T>C		intron_variant		1		ENSP00000412934.2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57061 AN: 151818 Hom.: 11461 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.376 AC: 57084 AN: 151936 Hom.: 11459 Cov.: 31 AF XY: 0.374 AC XY: 27731 AN XY: 74246

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.374

Alfa AF: 0.425 Hom.: 25361

Bravo AF: 0.358

Asia WGS AF: 0.302 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.68

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: rs9833771; hg19: chr3-32362998;