rs8014194

Positions:

• chr14-95254341-T-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CLMN	NM_024734.4	c.83-24208A>T		intron_variant		ENST00000298912.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLMN	ENST00000298912.9	c.83-24208A>T		intron_variant		1	NM_024734.4	P1
CLMN	ENST00000555336.6	c.-123+6174A>T		intron_variant		5
CLMN	ENST00000555615.1	c.-122-24208A>T		intron_variant		5
CLMN	ENST00000553733.1	c.83-24208A>T		intron_variant, NMD_transcript_variant		4

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

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.302

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

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: rs8014194; hg19: chr14-95720678;