8-38173827-A-G

Variant names:

• chr8-38173827-A-G
• rs16887244
• NM_014462.3:c.47-1794T>C

Variant summary

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

The NM_014462.3(LSM1):​c.47-1794T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,190 control chromosomes in the GnomAD database, including 3,508 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 0.20 (3508 hom., cov: 32)
• Consequence: LSM1 NM_014462.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 51 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM1	NM_014462.3	MANE Select	c.47-1794T>C		intron	N/A	NP_055277.1
	LSM1	NR_045492.2		n.220-1794T>C		intron	N/A
	LSM1	NR_045493.1		n.179-1794T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM1	ENST00000311351.9	TSL:1 MANE Select	c.47-1794T>C		intron	N/A	ENSP00000310596.4
	LSM1	ENST00000520755.5	TSL:1	c.47-1794T>C		intron	N/A	ENSP00000430021.1
	LSM1	ENST00000520286.5	TSL:1	n.179-1794T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31160 AN: 152072 Hom.: 3505 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.205 AC: 31173 AN: 152190 Hom.: 3508 Cov.: 32 AF XY: 0.201 AC XY: 14932 AN XY: 74412

African (AFR) AF: 0.147 AC: 6097 AN: 41542

American (AMR) AF: 0.190 AC: 2905 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 591 AN: 3470

East Asian (EAS) AF: 0.309 AC: 1599 AN: 5174

South Asian (SAS) AF: 0.117 AC: 565 AN: 4828

European-Finnish (FIN) AF: 0.193 AC: 2044 AN: 10596

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16536 AN: 67990

Other (OTH) AF: 0.205 AC: 433 AN: 2110

Alfa AF: 0.230 Hom.: 18940

Bravo AF: 0.208

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.64
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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

Other links and lift over

dbSNP: rs16887244; hg19: chr8-38031345;