NM_006369.5:c.357+1739A>G

Variant names:

• chr1-46295824-T-C
• rs10890388
• NM_006369.5:c.357+1739A>G

Variant summary

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

The NM_006369.5(LRRC41):​c.357+1739A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,128 control chromosomes in the GnomAD database, including 39,700 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 0.72 (39700 hom., cov: 33)
• Consequence: LRRC41 NM_006369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.605
• Publications: 6 publications found

Genes affected

LRRC41 (HGNC:16917): (leucine rich repeat containing 41) Predicted to enable identical protein binding activity. Predicted to be involved in protein ubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC41	NM_006369.5	c.357+1739A>G		intron_variant	Intron 3 of 9	ENST00000617190.5	NP_006360.3
LRRC41	XM_047431688.1	c.381+1739A>G		intron_variant	Intron 3 of 7		XP_047287644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC41	ENST00000617190.5	c.357+1739A>G		intron_variant	Intron 3 of 9	1	NM_006369.5	ENSP00000477792.1
LRRC41	ENST00000498402.2	n.291+1739A>G		intron_variant	Intron 3 of 4	2		ENSP00000483633.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109447 AN: 152010 Hom.: 39684 Cov.: 33

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.720 AC: 109514 AN: 152128 Hom.: 39700 Cov.: 33 AF XY: 0.721 AC XY: 53581 AN XY: 74358

African (AFR) AF: 0.631 AC: 26157 AN: 41480

American (AMR) AF: 0.703 AC: 10745 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2911 AN: 3468

East Asian (EAS) AF: 0.807 AC: 4178 AN: 5180

South Asian (SAS) AF: 0.757 AC: 3649 AN: 4822

European-Finnish (FIN) AF: 0.731 AC: 7739 AN: 10580

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51595 AN: 67996

Other (OTH) AF: 0.738 AC: 1558 AN: 2112

Alfa AF: 0.743 Hom.: 34275

Bravo AF: 0.714

Asia WGS AF: 0.788 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.56
PhyloP100		-0.60
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: rs10890388; hg19: chr1-46761496;