11-40246547-C-T

Variant names:

• chr11-40246547-C-T
• rs7125624
• NM_001258419.2:c.-175-4949G>A

Variant summary

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

The NM_020929.3(LRRC4C):​c.-96+73081G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,964 control chromosomes in the GnomAD database, including 46,214 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 0.75 (46214 hom., cov: 31)
• Consequence: LRRC4C NM_020929.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16
• Publications: 1 publications found

Genes affected

LRRC4C (HGNC:29317): (leucine rich repeat containing 4C) NGL1 is a specific binding partner for netrin G1 (NTNG1; MIM 608818), which is a member of the netrin family of axon guidance molecules (Lin et al., 2003 [PubMed 14595443]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020929.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	NM_001258419.2	MANE Select	c.-175-4949G>A		intron	N/A	NP_001245348.1
	LRRC4C	NM_020929.3		c.-96+73081G>A		intron	N/A	NP_065980.1
	LRRC4C	NR_047673.1		n.938+45646G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	ENST00000528697.6	TSL:1 MANE Select	c.-175-4949G>A		intron	N/A	ENSP00000437132.1
	LRRC4C	ENST00000278198.2	TSL:1	c.-43+45646G>A		intron	N/A	ENSP00000278198.1
	LRRC4C	ENST00000527150.5	TSL:1	c.-96+45646G>A		intron	N/A	ENSP00000436976.1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113358 AN: 151846 Hom.: 46215 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.746 AC: 113384 AN: 151964 Hom.: 46214 Cov.: 31 AF XY: 0.750 AC XY: 55677 AN XY: 74282

African (AFR) AF: 0.382 AC: 15810 AN: 41348

American (AMR) AF: 0.842 AC: 12852 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3012 AN: 3472

East Asian (EAS) AF: 0.954 AC: 4921 AN: 5158

South Asian (SAS) AF: 0.858 AC: 4124 AN: 4806

European-Finnish (FIN) AF: 0.852 AC: 9016 AN: 10588

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.895 AC: 60888 AN: 68008

Other (OTH) AF: 0.793 AC: 1674 AN: 2110

Alfa AF: 0.852 Hom.: 24791

Bravo AF: 0.730

Asia WGS AF: 0.878 AC: 3051 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.075
DANN	Benign	0.61
PhyloP100		-3.2
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: rs7125624; hg19: chr11-40268097;