14-95270110-C-T

Position:

• chr14-95270110-C-T

Variant summary

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

The ENST00000298912.9(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 ENST00000298912.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761

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 (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLMN	NM_024734.4	c.83-39977G>A		intron_variant		ENST00000298912.9	NP_079010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLMN	ENST00000298912.9	c.83-39977G>A		intron_variant		1	NM_024734.4	ENSP00000298912	P1
CLMN	ENST00000555336.6	c.-210-9508G>A		intron_variant		5		ENSP00000451705
CLMN	ENST00000555615.1	c.-123+37404G>A		intron_variant		5		ENSP00000452525
CLMN	ENST00000553733.1	c.83-39977G>A		intron_variant, NMD_transcript_variant		4		ENSP00000451189

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

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.0806

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.0440

Gnomad4 NFE AF: 0.0448

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0566 Hom.: 571

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

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: rs1884535; hg19: chr14-95736447;