14-95205534-G-T

Variant names:

• chr14-95205534-G-T
• rs1187614
• NM_024734.4:c.886-1071C>A

Variant summary

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

The NM_024734.4(CLMN):​c.886-1071C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,044 control chromosomes in the GnomAD database, including 7,755 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 0.29 (7755 hom., cov: 32)
• Consequence: CLMN NM_024734.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797
• Publications: 9 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024734.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLMN	NM_024734.4	MANE Select	c.886-1071C>A		intron	N/A	NP_079010.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLMN	ENST00000298912.9	TSL:1 MANE Select	c.886-1071C>A		intron	N/A	ENSP00000298912.3
	CLMN	ENST00000556454.1	TSL:2	n.250-1071C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43338 AN: 151926 Hom.: 7733 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.285 AC: 43400 AN: 152044 Hom.: 7755 Cov.: 32 AF XY: 0.288 AC XY: 21364 AN XY: 74306

African (AFR) AF: 0.496 AC: 20554 AN: 41458

American (AMR) AF: 0.255 AC: 3904 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3468

East Asian (EAS) AF: 0.432 AC: 2234 AN: 5176

South Asian (SAS) AF: 0.214 AC: 1031 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2375 AN: 10550

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11361 AN: 67980

Other (OTH) AF: 0.281 AC: 591 AN: 2106

Alfa AF: 0.238 Hom.: 7944

Bravo AF: 0.300

Asia WGS AF: 0.336 AC: 1166 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.43
PhyloP100		-0.80
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: rs1187614; hg19: chr14-95671871;