chr1-100167913-T-A

Variant names:

• chr1-100167913-T-A
• rs6677080
• NM_144620.4:c.113+491A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000285530 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LRRC39	NM_144620.4	c.113+491A>T		intron_variant	Intron 3 of 9	ENST00000370137.6	NP_653221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC39	ENST00000370137.6	c.113+491A>T		intron_variant	Intron 3 of 9	1	NM_144620.4	ENSP00000359156.1
LRRC39	ENST00000370138.1	c.113+491A>T		intron_variant	Intron 3 of 10	5		ENSP00000359157.1
LRRC39	ENST00000342895.8	c.113+491A>T		intron_variant	Intron 3 of 9	5		ENSP00000344470.3
ENSG00000285530	ENST00000835180.1	n.139+970T>A		intron_variant	Intron 2 of 4

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

African (AFR) AF: 0.406 AC: 16774 AN: 41346

American (AMR) AF: 0.120 AC: 1829 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3470

East Asian (EAS) AF: 0.0488 AC: 253 AN: 5180

South Asian (SAS) AF: 0.0990 AC: 476 AN: 4808

European-Finnish (FIN) AF: 0.0906 AC: 945 AN: 10436

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9185 AN: 67896

Other (OTH) AF: 0.173 AC: 365 AN: 2104

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
PhyloP100		-0.031
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: rs6677080; hg19: chr1-100633469;