rs1338623

Variant names:

• chr1-205420750-C-G
• rs1338623
• NM_001199050.2:c.-38-176G>C

Variant summary

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

The NM_001199050.2(LEMD1):​c.-38-176G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 152,288 control chromosomes in the GnomAD database, including 102 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 0.026 (102 hom., cov: 32)
• Consequence: LEMD1 NM_001199050.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 1 publications found

Genes affected

LEMD1 (HGNC:18725): (LEM domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LEMD1-AS1 (HGNC:44132): (LEMD1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LEMD1	NM_001199050.2	c.-38-176G>C		intron_variant	Intron 1 of 5	ENST00000367153.9	NP_001185979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LEMD1	ENST00000367153.9	c.-38-176G>C		intron_variant	Intron 1 of 5	1	NM_001199050.2	ENSP00000356121.4

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3988 AN: 152170 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.00923

Gnomad SAS AF: 0.00827

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00648

Gnomad OTH AF: 0.0187

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

GnomAD4 genome AF: 0.0262 AC: 3993 AN: 152288 Hom.: 102 Cov.: 32 AF XY: 0.0278 AC XY: 2067 AN XY: 74456

African (AFR) AF: 0.0623 AC: 2591 AN: 41566

American (AMR) AF: 0.0119 AC: 182 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3470

East Asian (EAS) AF: 0.00925 AC: 48 AN: 5188

South Asian (SAS) AF: 0.00828 AC: 40 AN: 4830

European-Finnish (FIN) AF: 0.0523 AC: 554 AN: 10596

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00648 AC: 441 AN: 68030

Other (OTH) AF: 0.0176 AC: 37 AN: 2106

Alfa AF: 0.0183 Hom.: 9

Bravo AF: 0.0257

Asia WGS AF: 0.0200 AC: 71 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	11
DANN	Benign	0.69
PhyloP100		0.38
PromoterAI		0.0070	Neutral
Mutation Taster		=100/0	polymorphism

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: rs1338623; hg19: chr1-205389878;