rs2282276

Positions:

• chr14-95194792-T-C

Variant summary

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

The NM_024734.4(CLMN):​c.2709-196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,216 control chromosomes in the GnomAD database, including 1,591 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 0.13 (1591 hom., cov: 33)
• Consequence: CLMN NM_024734.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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 = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLMN	NM_024734.4	c.2709-196A>G		intron_variant		ENST00000298912.9	NP_079010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLMN	ENST00000298912.9	c.2709-196A>G		intron_variant		1	NM_024734.4	ENSP00000298912	P1
CLMN	ENST00000556454.1	n.2073-196A>G		intron_variant, non_coding_transcript_variant		2
CLMN	ENST00000557696.5	n.88-196A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19502 AN: 152100 Hom.: 1584 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0792

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.128 AC: 19549 AN: 152216 Hom.: 1591 Cov.: 33 AF XY: 0.133 AC XY: 9876 AN XY: 74404

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.0812

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0792

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0940 Hom.: 547

Bravo AF: 0.127

Asia WGS AF: 0.259 AC: 898 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	4.8
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2282276; hg19: chr14-95661129;