rs4955272

Positions:

• chr3-32272184-G-A

Variant summary

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

The NM_178868.5(CMTM8):​c.147+33065G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,118 control chromosomes in the GnomAD database, including 3,962 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 0.21 (3962 hom., cov: 33)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM8	NM_178868.5	c.147+33065G>A		intron_variant		ENST00000307526.4	NP_849199.2
CMTM8	NM_001320308.2	c.147+33065G>A		intron_variant			NP_001307237.1
CMTM8	XM_011533416.4	c.148-10407G>A		intron_variant			XP_011531718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTM8	ENST00000307526.4	c.147+33065G>A		intron_variant		1	NM_178868.5	ENSP00000307741	P1
CMTM8	ENST00000458535.6	c.147+33065G>A		intron_variant		1		ENSP00000412934

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31366 AN: 152000 Hom.: 3967 Cov.: 33

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.206 AC: 31352 AN: 152118 Hom.: 3962 Cov.: 33 AF XY: 0.203 AC XY: 15093 AN XY: 74356

Gnomad4 AFR AF: 0.0696

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.223

Alfa AF: 0.267 Hom.: 5669

Bravo AF: 0.195

Asia WGS AF: 0.137 AC: 477 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.83

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: rs4955272; hg19: chr3-32313676;