19-18322415-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSM4	NM_012321.5	c.3+603A>G		intron_variant	Intron 1 of 4	ENST00000593829.6	NP_036453.1
LSM4	NM_001252129.2	c.3+603A>G		intron_variant	Intron 1 of 3		NP_001239058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSM4	ENST00000593829.6	c.3+603A>G		intron_variant	Intron 1 of 4	1	NM_012321.5	ENSP00000469468.2

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

Gnomad4 AFR AF: 0.969

Gnomad4 AMR AF: 0.885

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.880

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.872

Alfa AF: 0.884 Hom.: 38280

Bravo AF: 0.907

Asia WGS AF: 0.839 AC: 2918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.44
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs2241351; hg19: chr19-18433225;