rs278997

Positions:

• chr12-25614807-G-A

Variant summary

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

The NM_001352232.2(LMNTD1):​c.-282-30196C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0926 in 152,066 control chromosomes in the GnomAD database, including 1,043 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 0.093 (1043 hom., cov: 31)
• Consequence: LMNTD1 NM_001352232.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMNTD1	NM_001352232.2	c.-282-30196C>T		intron_variant			NP_001339161.1
LMNTD1	NM_001352233.2	c.-91-32344C>T		intron_variant			NP_001339162.1
LMNTD1	NM_001352234.2	c.-50+33687C>T		intron_variant			NP_001339163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMNTD1	ENST00000445693.5	c.58+33687C>T		intron_variant		2		ENSP00000407043.1
LMNTD1	ENST00000538178.5	c.-50+15788C>T		intron_variant		3		ENSP00000442871.1
LMNTD1	ENST00000540106.5	c.-50+33687C>T		intron_variant		4		ENSP00000445242.1

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14080 AN: 151948 Hom.: 1045 Cov.: 31

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.0415

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0501

Gnomad OTH AF: 0.0864

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

GnomAD4 genome AF: 0.0926 AC: 14084 AN: 152066 Hom.: 1043 Cov.: 31 AF XY: 0.0905 AC XY: 6723 AN XY: 74322

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0561

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.0416

Gnomad4 SAS AF: 0.0486

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0501

Gnomad4 OTH AF: 0.0855

Alfa AF: 0.0656 Hom.: 162

Bravo AF: 0.0994

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.34
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs278997; hg19: chr12-25767741;