rs11914777

Variant names:

• chr3-32292516-T-C
• rs11914777
• NM_178868.5:c.147+53397T>C

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+53397T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,090 control chromosomes in the GnomAD database, including 33,911 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 0.66 (33911 hom., cov: 32)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMTM8	NM_178868.5	c.147+53397T>C		intron_variant	Intron 1 of 3	ENST00000307526.4	NP_849199.2
CMTM8	NM_001320308.2	c.147+53397T>C		intron_variant	Intron 1 of 2		NP_001307237.1
CMTM8	XM_011533416.4	c.216+9857T>C		intron_variant	Intron 3 of 5		XP_011531718.1
CMTM8	XM_017005779.2	c.18+361T>C		intron_variant	Intron 1 of 3		XP_016861268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMTM8	ENST00000307526.4	c.147+53397T>C		intron_variant	Intron 1 of 3	1	NM_178868.5	ENSP00000307741.3
CMTM8	ENST00000458535.6	c.147+53397T>C		intron_variant	Intron 1 of 2	1		ENSP00000412934.2

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100847 AN: 151972 Hom.: 33879 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.664 AC: 100945 AN: 152090 Hom.: 33911 Cov.: 32 AF XY: 0.667 AC XY: 49590 AN XY: 74366

African (AFR) AF: 0.731 AC: 30337 AN: 41490

American (AMR) AF: 0.721 AC: 11004 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1955 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4054 AN: 5170

South Asian (SAS) AF: 0.577 AC: 2785 AN: 4824

European-Finnish (FIN) AF: 0.658 AC: 6950 AN: 10566

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41642 AN: 67982

Other (OTH) AF: 0.663 AC: 1401 AN: 2114

Alfa AF: 0.628 Hom.: 49367

Bravo AF: 0.678

Asia WGS AF: 0.661 AC: 2296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.068
DANN	Benign	0.30
PhyloP100		-2.1
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: rs11914777; hg19: chr3-32334008;