rs8014194

Variant names:

• chr14-95254341-T-A
• rs8014194
• NM_024734.4:c.83-24208A>T

Variant summary

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

The NM_024734.4(CLMN):​c.83-24208A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,038 control chromosomes in the GnomAD database, including 9,420 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 0.33 (9420 hom., cov: 32)
• Consequence: CLMN NM_024734.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.609
• Publications: 18 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLMN	NM_024734.4	c.83-24208A>T		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.83-24208A>T		intron_variant	Intron 1 of 12	1	NM_024734.4	ENSP00000298912.3
CLMN	ENST00000555336.6	c.-123+6174A>T		intron_variant	Intron 2 of 6	5		ENSP00000451705.1
CLMN	ENST00000555615.1	c.-122-24208A>T		intron_variant	Intron 1 of 5	5		ENSP00000452525.1
CLMN	ENST00000553733.1	n.83-24208A>T		intron_variant	Intron 1 of 4	4		ENSP00000451189.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49663 AN: 151920 Hom.: 9392 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.327 AC: 49751 AN: 152038 Hom.: 9420 Cov.: 32 AF XY: 0.324 AC XY: 24046 AN XY: 74320

African (AFR) AF: 0.525 AC: 21757 AN: 41428

American (AMR) AF: 0.260 AC: 3968 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3470

East Asian (EAS) AF: 0.141 AC: 729 AN: 5174

South Asian (SAS) AF: 0.297 AC: 1430 AN: 4822

European-Finnish (FIN) AF: 0.269 AC: 2847 AN: 10578

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17269 AN: 67978

Other (OTH) AF: 0.302 AC: 638 AN: 2116

Alfa AF: 0.262 Hom.: 3040

Bravo AF: 0.329

Asia WGS AF: 0.272 AC: 942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.42
PhyloP100		-0.61
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: rs8014194; hg19: chr14-95720678;