chr12-25642173-T-C

Variant names:

• chr12-25642173-T-C
• rs7970954
• NM_001352232.2:c.-283+6321A>G

Variant summary

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

The NM_001352232.2(LMNTD1):​c.-283+6321A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,992 control chromosomes in the GnomAD database, including 19,986 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 0.48 (19986 hom., cov: 31)
• Consequence: LMNTD1 NM_001352232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 4 publications found

Genes affected

LMNTD1 (HGNC:26683): (lamin tail domain containing 1) Predicted to act upstream of or within cell population proliferation. Predicted to be located in nucleus. Predicted to be active in cytoplasm and nuclear envelope. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352232.2. 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
	LMNTD1	NM_001352232.2		c.-283+6321A>G		intron	N/A	NP_001339161.1
	LMNTD1	NM_001352233.2		c.-92+6321A>G		intron	N/A	NP_001339162.1
	LMNTD1	NM_001352234.2		c.-50+6321A>G		intron	N/A	NP_001339163.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNTD1	ENST00000445693.5	TSL:2	c.58+6321A>G		intron	N/A	ENSP00000407043.1
	LMNTD1	ENST00000540106.5	TSL:4	c.-50+6321A>G		intron	N/A	ENSP00000445242.1
	LMNTD1	ENST00000545543.1	TSL:3	c.-83+6321A>G		intron	N/A	ENSP00000443596.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72964 AN: 151874 Hom.: 19993 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.480 AC: 72976 AN: 151992 Hom.: 19986 Cov.: 31 AF XY: 0.478 AC XY: 35480 AN XY: 74300

African (AFR) AF: 0.220 AC: 9142 AN: 41464

American (AMR) AF: 0.540 AC: 8235 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1549 AN: 3468

East Asian (EAS) AF: 0.285 AC: 1476 AN: 5170

South Asian (SAS) AF: 0.507 AC: 2439 AN: 4810

European-Finnish (FIN) AF: 0.547 AC: 5766 AN: 10534

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42610 AN: 67980

Other (OTH) AF: 0.506 AC: 1063 AN: 2102

Alfa AF: 0.577 Hom.: 100076

Bravo AF: 0.468

Asia WGS AF: 0.407 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.57
PhyloP100		0.027
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7970954; hg19: chr12-25795107;