NM_178868.5:c.147+39797G>T

Variant names:

• chr3-32278916-G-T
• rs7644602
• NM_178868.5:c.147+39797G>T

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+39797G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,904 control chromosomes in the GnomAD database, including 22,304 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 0.53 (22304 hom., cov: 31)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMTM8	NM_178868.5	c.147+39797G>T		intron_variant	Intron 1 of 3	ENST00000307526.4	NP_849199.2
CMTM8	NM_001320308.2	c.147+39797G>T		intron_variant	Intron 1 of 2		NP_001307237.1
CMTM8	XM_011533416.4	c.148-3675G>T		intron_variant	Intron 2 of 5		XP_011531718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMTM8	ENST00000307526.4	c.147+39797G>T		intron_variant	Intron 1 of 3	1	NM_178868.5	ENSP00000307741.3
CMTM8	ENST00000458535.6	c.147+39797G>T		intron_variant	Intron 1 of 2	1		ENSP00000412934.2

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80597 AN: 151786 Hom.: 22298 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.531 AC: 80634 AN: 151904 Hom.: 22304 Cov.: 31 AF XY: 0.537 AC XY: 39844 AN XY: 74228

African (AFR) AF: 0.380 AC: 15732 AN: 41408

American (AMR) AF: 0.549 AC: 8385 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2151 AN: 3472

East Asian (EAS) AF: 0.876 AC: 4511 AN: 5148

South Asian (SAS) AF: 0.607 AC: 2925 AN: 4820

European-Finnish (FIN) AF: 0.602 AC: 6348 AN: 10544

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.570 AC: 38705 AN: 67930

Other (OTH) AF: 0.542 AC: 1144 AN: 2112

Alfa AF: 0.555 Hom.: 52286

Bravo AF: 0.522

Asia WGS AF: 0.717 AC: 2494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.1
DANN	Benign	0.72
PhyloP100		0.39
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: rs7644602; hg19: chr3-32320408;