1-100167913-T-A

Position:

• chr1-100167913-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144620.4(LRRC39):​c.113+491A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 151,656 control chromosomes in the GnomAD database, including 4,362 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 (4362 hom., cov: 31)
• Consequence: LRRC39 NM_144620.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

Genes affected

LRRC39 (HGNC:28228): (leucine rich repeat containing 39) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Predicted to be located in M band. Predicted to be active in cytoplasm and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC39	NM_144620.4	c.113+491A>T		intron_variant		ENST00000370137.6	NP_653221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC39	ENST00000370137.6	c.113+491A>T		intron_variant		1	NM_144620.4	ENSP00000359156	P1
LRRC39	ENST00000342895.8	c.113+491A>T		intron_variant		5		ENSP00000344470	P1
LRRC39	ENST00000370138.1	c.113+491A>T		intron_variant		5		ENSP00000359157

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30335 AN: 151548 Hom.: 4344 Cov.: 31

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0485

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.200 AC: 30394 AN: 151656 Hom.: 4362 Cov.: 31 AF XY: 0.195 AC XY: 14478 AN XY: 74150

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.0488

Gnomad4 SAS AF: 0.0990

Gnomad4 FIN AF: 0.0906

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.173

Alfa AF: 0.175 Hom.: 374

Bravo AF: 0.210

Asia WGS AF: 0.113 AC: 391 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.71

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: rs6677080; hg19: chr1-100633469;