rs6803740

Positions:

• chr3-32302814-A-G

Variant summary

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

The NM_178868.5(CMTM8):​c.148-54559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,170 control chromosomes in the GnomAD database, including 2,042 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 0.16 (2042 hom., cov: 32)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM8	NM_178868.5	c.148-54559A>G		intron_variant		ENST00000307526.4	NP_849199.2
CMTM8	NM_001320308.2	c.147+63695A>G		intron_variant			NP_001307237.1
CMTM8	XM_011533416.4	c.216+20155A>G		intron_variant			XP_011531718.1
CMTM8	XM_017005779.2	c.18+10659A>G		intron_variant			XP_016861268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTM8	ENST00000307526.4	c.148-54559A>G		intron_variant		1	NM_178868.5	ENSP00000307741.3
CMTM8	ENST00000458535.6	c.147+63695A>G		intron_variant		1		ENSP00000412934.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24442 AN: 152052 Hom.: 2047 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.161 AC: 24448 AN: 152170 Hom.: 2042 Cov.: 32 AF XY: 0.163 AC XY: 12110 AN XY: 74392

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.166

Alfa AF: 0.174 Hom.: 4846

Bravo AF: 0.151

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.55

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: rs6803740; hg19: chr3-32344306;