rs7823144

Variant names:

• chr8-38170677-G-A
• rs7823144
• NM_014462.3:c.116-760C>T

Variant summary

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

The NM_014462.3(LSM1):​c.116-760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,026 control chromosomes in the GnomAD database, including 2,753 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 0.16 (2753 hom., cov: 32)
• Consequence: LSM1 NM_014462.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 5 publications found

Genes affected

LSM1 (HGNC:20472): (LSM1 homolog, mRNA degradation associated) This gene encodes a member of the LSm family of RNA-binding proteins. LSm proteins form stable heteromers that bind specifically to the 3'-terminal oligo(U) tract of U6 snRNA and may play a role in pre-mRNA splicing by mediating U4/U6 snRNP formation. Increased expression of this gene may play a role in cellular transformation and the progression of several malignancies including lung cancer, mesothelioma and breast cancer. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Nov 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014462.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM1	NM_014462.3	MANE Select	c.116-760C>T		intron	N/A	NP_055277.1	A0A0S2Z590
	LSM1	NR_045492.2		n.288+1288C>T		intron	N/A
	LSM1	NR_045493.1		n.248-760C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM1	ENST00000311351.9	TSL:1 MANE Select	c.116-760C>T		intron	N/A	ENSP00000310596.4	O15116
	LSM1	ENST00000520755.5	TSL:1	c.115+1288C>T		intron	N/A	ENSP00000430021.1	E5RH18
	LSM1	ENST00000520286.5	TSL:1	n.248-760C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24775 AN: 151908 Hom.: 2741 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0400

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.163 AC: 24830 AN: 152026 Hom.: 2753 Cov.: 32 AF XY: 0.168 AC XY: 12453 AN XY: 74318

African (AFR) AF: 0.301 AC: 12468 AN: 41442

American (AMR) AF: 0.151 AC: 2312 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 139 AN: 3472

East Asian (EAS) AF: 0.292 AC: 1504 AN: 5158

South Asian (SAS) AF: 0.167 AC: 807 AN: 4820

European-Finnish (FIN) AF: 0.168 AC: 1776 AN: 10556

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0812 AC: 5518 AN: 67994

Other (OTH) AF: 0.126 AC: 265 AN: 2108

Alfa AF: 0.0998 Hom.: 1766

Bravo AF: 0.165

Asia WGS AF: 0.224 AC: 781 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	17
DANN	Benign	0.71
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7823144;

hg19: chr8-38028195;