19-18322415-T-C

Variant names:

• chr19-18322415-T-C
• rs2241351
• NM_012321.5:c.3+603A>G

Variant summary

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

The NM_012321.5(LSM4):​c.3+603A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,098 control chromosomes in the GnomAD database, including 62,185 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 0.90 (62185 hom., cov: 30)
• Consequence: LSM4 NM_012321.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13
• Publications: 3 publications found

Genes affected

LSM4 (HGNC:17259): (LSM4 homolog, U6 small nuclear RNA and 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. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012321.5. 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
	LSM4	NM_012321.5	MANE Select	c.3+603A>G		intron	N/A	NP_036453.1
	LSM4	NM_001252129.2		c.3+603A>G		intron	N/A	NP_001239058.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSM4	ENST00000593829.6	TSL:1 MANE Select	c.3+603A>G		intron	N/A	ENSP00000469468.2
	LSM4	ENST00000594828.7	TSL:2	c.3+603A>G		intron	N/A	ENSP00000477443.1
	LSM4	ENST00000252816.10	TSL:2	c.3+603A>G		intron	N/A	ENSP00000475950.1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137251 AN: 151980 Hom.: 62131 Cov.: 30

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.903 AC: 137352 AN: 152098 Hom.: 62185 Cov.: 30 AF XY: 0.903 AC XY: 67097 AN XY: 74344

African (AFR) AF: 0.969 AC: 40208 AN: 41506

American (AMR) AF: 0.885 AC: 13522 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3150 AN: 3470

East Asian (EAS) AF: 0.858 AC: 4428 AN: 5162

South Asian (SAS) AF: 0.880 AC: 4243 AN: 4822

European-Finnish (FIN) AF: 0.882 AC: 9325 AN: 10570

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59550 AN: 67974

Other (OTH) AF: 0.872 AC: 1840 AN: 2110

Alfa AF: 0.891 Hom.: 87588

Bravo AF: 0.907

Asia WGS AF: 0.839 AC: 2918 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	0.44
DANN	Benign	0.50
PhyloP100		-3.1
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

Other links and lift over

dbSNP: rs2241351; hg19: chr19-18433225;