16-66573285-A-G

Position:

• chr16-66573285-A-G

Variant summary

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

The NM_052999.4(CMTM1):​c.591+3191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,174 control chromosomes in the GnomAD database, including 5,965 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 0.25 (5965 hom., cov: 32)
• Consequence: CMTM1 NM_052999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889

Genes affected

CMTM1 (HGNC:19172): (CKLF like MARVEL transmembrane domain containing 1) This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and the transmembrane 4 superfamilies of signaling molecules. The protein encoded by this gene may play an important role in testicular development. Alternatively spliced transcript variants encoding different isoforms have been identified. Naturally occurring read-through transcription occurs between this locus and the neighboring locus CKLF (chemokine-like factor).[provided by RefSeq, Feb 2011]

CKLF-CMTM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM1	NM_052999.4	c.591+3191A>G		intron_variant		ENST00000379500.7	NP_443725.3
CKLF-CMTM1	NM_001204099.2	c.238-3819A>G		intron_variant			NP_001191028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTM1	ENST00000379500.7	c.591+3191A>G		intron_variant		1	NM_052999.4	ENSP00000368814	P2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38089 AN: 152056 Hom.: 5963 Cov.: 32

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.250 AC: 38086 AN: 152174 Hom.: 5965 Cov.: 32 AF XY: 0.254 AC XY: 18928 AN XY: 74398

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.279

Alfa AF: 0.310 Hom.: 10661

Bravo AF: 0.236

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.74

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: rs896086; hg19: chr16-66607188;