rs1187614

chr14-95205534-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLMN	NM_024734.4	c.886-1071C>A		intron_variant		ENST00000298912.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLMN	ENST00000298912.9	c.886-1071C>A		intron_variant		1	NM_024734.4	P1
CLMN	ENST00000556454.1	n.250-1071C>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.281

Alfa AF: 0.208 Hom.: 2905

Bravo AF: 0.300

Asia WGS AF: 0.336 AC: 1166 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.18
Dann	Benign	0.43

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: rs1187614; hg19: chr14-95671871;