rs115102486

chr14-95298227-A-G

Variant summary

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

The NM_024734.4(CLMN):c.82+21484T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 151,420 control chromosomes in the GnomAD database, including 445 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 0.053 (445 hom., cov: 32)
• Consequence: CLMN NM_024734.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLMN	NM_024734.4	c.82+21484T>C		intron_variant		ENST00000298912.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLMN	ENST00000298912.9	c.82+21484T>C		intron_variant		1	NM_024734.4	P1
CLMN	ENST00000555615.1	c.-123+9287T>C		intron_variant		5
CLMN	ENST00000553733.1	c.82+21484T>C		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8062 AN: 151302 Hom.: 445 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.00214

Gnomad SAS AF: 0.00856

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0448

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

GnomAD4 genome AF: 0.0533 AC: 8076 AN: 151420 Hom.: 445 Cov.: 32 AF XY: 0.0508 AC XY: 3754 AN XY: 73954

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.00215

Gnomad4 SAS AF: 0.00877

Gnomad4 FIN AF: 0.0223

Gnomad4 NFE AF: 0.0231

Gnomad4 OTH AF: 0.0444

Alfa AF: 0.0437 Hom.: 41

Bravo AF: 0.0573

Asia WGS AF: 0.0160 AC: 54 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	0.23
Dann	Benign	0.75

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: rs115102486; hg19: chr14-95764564;