7-118188313-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_016200.5(LSM8):c.108G>A(p.Leu36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,613,484 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00074 (16 hom.)
• Consequence: LSM8 NM_016200.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.52

Genes affected

LSM8 (HGNC:20471): (LSM8 homolog, U6 small nuclear RNA associated) This gene encodes a member of the like-Sm family of proteins. The encoded protein consists of a closed barrel shape, made up of five anti-parallel beta strands and an alpha helix. This protein partners with six paralogs to form a heteroheptameric ring which transiently binds U6 small nuclear RNAs and is involved in the general maturation of RNA in the nucleus. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 7-118188313-G-A is Benign according to our data. Variant chr7-118188313-G-A is described in ClinVar as [Benign]. Clinvar id is 784116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.52 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00643 (979/152248) while in subpopulation AFR AF= 0.022 (914/41532). AF 95% confidence interval is 0.0208. There are 8 homozygotes in gnomad4. There are 459 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LSM8	NM_016200.5	c.108G>A	p.Leu36=	synonymous_variant	3/4	ENST00000249299.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSM8	ENST00000249299.7	c.108G>A	p.Leu36=	synonymous_variant	3/4	1	NM_016200.5	P1
LSM8	ENST00000422760.1	c.45G>A	p.Leu15=	synonymous_variant	2/3	1
LSM8	ENST00000424702.1	c.108G>A	p.Leu36=	synonymous_variant	3/3	1
LSM8	ENST00000411938.1	c.141G>A	p.Leu47=	synonymous_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.00643 AC: 978 AN: 152130 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00178 AC: 448 AN: 251398 Hom.: 2 AF XY: 0.00119 AC XY: 162 AN XY: 135880

Gnomad AFR exome AF: 0.0236

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000741 AC: 1083 AN: 1461236 Hom.: 16 Cov.: 30 AF XY: 0.000620 AC XY: 451 AN XY: 726968

Gnomad4 AFR exome AF: 0.0263

Gnomad4 AMR exome AF: 0.00172

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.00166

GnomAD4 genome AF: 0.00643 AC: 979 AN: 152248 Hom.: 8 Cov.: 33 AF XY: 0.00617 AC XY: 459 AN XY: 74448

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00279 Hom.: 2

Bravo AF: 0.00786

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	11
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35949266; hg19: chr7-117828367;