14-95270110-C-T

Variant names:

• chr14-95270110-C-T
• rs1884535
• NM_024734.4:c.83-39977G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024734.4(CLMN):​c.83-39977G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 152,210 control chromosomes in the GnomAD database, including 1,156 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 0.075 (1156 hom., cov: 32)
• Consequence: CLMN NM_024734.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761
• Publications: 1 publications found

Genes affected

CLMN (HGNC:19972): (calmin) Predicted to enable actin filament binding activity. Predicted to be involved in negative regulation of cell population proliferation and nuclear migration. Predicted to act upstream of or within neuron projection development. Predicted to be integral component of membrane. Predicted to be part of meiotic nuclear membrane microtubule tethering complex. Predicted to be active in cytoplasm and nuclear outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLMN	NM_024734.4	c.83-39977G>A		intron_variant	Intron 1 of 12	ENST00000298912.9	NP_079010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLMN	ENST00000298912.9	c.83-39977G>A		intron_variant	Intron 1 of 12	1	NM_024734.4	ENSP00000298912.3
CLMN	ENST00000555336.6	c.-210-9508G>A		intron_variant	Intron 1 of 6	5		ENSP00000451705.1
CLMN	ENST00000555615.1	c.-123+37404G>A		intron_variant	Intron 1 of 5	5		ENSP00000452525.1
CLMN	ENST00000553733.1	n.83-39977G>A		intron_variant	Intron 1 of 4	4		ENSP00000451189.1

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 11459 AN: 152092 Hom.: 1156 Cov.: 32

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0448

Gnomad OTH AF: 0.0904

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

GnomAD4 genome AF: 0.0752 AC: 11450 AN: 152210 Hom.: 1156 Cov.: 32 AF XY: 0.0823 AC XY: 6129 AN XY: 74430

African (AFR) AF: 0.0198 AC: 821 AN: 41526

American (AMR) AF: 0.222 AC: 3396 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0806 AC: 280 AN: 3472

East Asian (EAS) AF: 0.424 AC: 2196 AN: 5174

South Asian (SAS) AF: 0.206 AC: 994 AN: 4818

European-Finnish (FIN) AF: 0.0440 AC: 467 AN: 10616

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0448 AC: 3048 AN: 68010

Other (OTH) AF: 0.0885 AC: 187 AN: 2112

Alfa AF: 0.0617 Hom.: 1127

Bravo AF: 0.0891

Asia WGS AF: 0.276 AC: 957 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	1.4
DANN	Benign	0.32
PhyloP100		-0.76
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: rs1884535; hg19: chr14-95736447;