1-46281629-T-C

Position:

• chr1-46281629-T-C

Variant summary

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

The ENST00000617190.5(LRRC41):​c.1496-244A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,048 control chromosomes in the GnomAD database, including 4,547 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 0.23 (4547 hom., cov: 32)
• Consequence: LRRC41 ENST00000617190.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC41	NM_006369.5	c.1496-244A>G		intron_variant		ENST00000617190.5	NP_006360.3
LRRC41	XM_047431688.1	c.1520-244A>G		intron_variant			XP_047287644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC41	ENST00000617190.5	c.1496-244A>G		intron_variant		1	NM_006369.5	ENSP00000477792	P1
LRRC41	ENST00000343304.10	c.1496-244A>G		intron_variant		1		ENSP00000343298	P1
LRRC41	ENST00000615587.4	c.1430-244A>G		intron_variant		1		ENSP00000484752
LRRC41	ENST00000472710.2	c.1166-244A>G		intron_variant, NMD_transcript_variant		2		ENSP00000478135

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34855 AN: 151930 Hom.: 4550 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00907

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.229 AC: 34858 AN: 152048 Hom.: 4547 Cov.: 32 AF XY: 0.225 AC XY: 16726 AN XY: 74338

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.00928

Gnomad4 SAS AF: 0.0955

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.222

Alfa AF: 0.281 Hom.: 12064

Bravo AF: 0.220

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.5
DANN	Benign	0.86

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: rs12142240; hg19: chr1-46747301;