rs3814816

Positions:

• chr14-95185428-G-A
• chr14-95185428-G-C

Variant summary

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

The NM_024734.4(CLMN):​c.*6136C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 152,338 control chromosomes in the GnomAD database, including 965 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 0.098 (961 hom., cov: 31)
  • Exomes 𝑓: 0.13 (4 hom.)
• Consequence: CLMN NM_024734.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150

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]

ENSG00000259143 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLMN	NM_024734.4	c.*6136C>T		3_prime_UTR_variant	13/13	ENST00000298912.9	NP_079010.2
CLMN	XM_011537158.2	c.*6136C>T		3_prime_UTR_variant	14/14		XP_011535460.1
CLMN	XM_017021646.2	c.*6136C>T		3_prime_UTR_variant	14/14		XP_016877135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLMN	ENST00000298912	c.*6136C>T		3_prime_UTR_variant	13/13	1	NM_024734.4	ENSP00000298912.3
ENSG00000259143	ENST00000556796.1	n.370+57C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14913 AN: 152002 Hom.: 959 Cov.: 31

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0873

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.128 AC: 28 AN: 218 Hom.: 4 Cov.: 0 AF XY: 0.139 AC XY: 22 AN XY: 158

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0981 AC: 14918 AN: 152120 Hom.: 961 Cov.: 31 AF XY: 0.103 AC XY: 7690 AN XY: 74344

Gnomad4 AFR AF: 0.0754

Gnomad4 AMR AF: 0.0794

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0873

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0843 Hom.: 332

Bravo AF: 0.0937

Asia WGS AF: 0.235 AC: 813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.54

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: rs3814816; hg19: chr14-95651765; COSMIC: COSV54185388;