rs1370717

Variant names:

• chr3-32312895-G-A
• rs1370717
• NM_178868.5:c.148-44478G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-32312895-G-A
• chr3-32312895-G-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.148-44478G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,418 control chromosomes in the GnomAD database, including 12,962 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 0.39 (12962 hom., cov: 29)
• Consequence: CMTM8 NM_178868.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178868.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTM8	NM_178868.5	MANE Select	c.148-44478G>A		intron	N/A	NP_849199.2
	CMTM8	NM_001320308.2		c.148-54977G>A		intron	N/A	NP_001307237.1	Q8IZV2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTM8	ENST00000307526.4	TSL:1 MANE Select	c.148-44478G>A		intron	N/A	ENSP00000307741.3	Q8IZV2-1
	CMTM8	ENST00000458535.6	TSL:1	c.148-54977G>A		intron	N/A	ENSP00000412934.2	Q8IZV2-2
	CMTM8	ENST00000867234.1		c.261+2242G>A		intron	N/A	ENSP00000537293.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59676 AN: 151300 Hom.: 12962 Cov.: 29

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.394 AC: 59697 AN: 151418 Hom.: 12962 Cov.: 29 AF XY: 0.400 AC XY: 29595 AN XY: 73972

African (AFR) AF: 0.215 AC: 8853 AN: 41212

American (AMR) AF: 0.516 AC: 7850 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1652 AN: 3462

East Asian (EAS) AF: 0.715 AC: 3674 AN: 5136

South Asian (SAS) AF: 0.508 AC: 2435 AN: 4792

European-Finnish (FIN) AF: 0.419 AC: 4374 AN: 10442

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29302 AN: 67856

Other (OTH) AF: 0.420 AC: 885 AN: 2106

Alfa AF: 0.424 Hom.: 40006

Bravo AF: 0.398

Asia WGS AF: 0.562 AC: 1953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.87
DANN	Benign	0.43
PhyloP100		0.23
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: rs1370717; hg19: chr3-32354387;