NM_001258419.2:c.-43+6292A>G

Variant names:

• chr11-40134509-T-C
• rs7936167
• NM_001258419.2:c.-43+6292A>G

Variant summary

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

The NM_001258419.2(LRRC4C):​c.-43+6292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,958 control chromosomes in the GnomAD database, including 4,549 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 0.22 (4549 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258419.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	NM_001258419.2	MANE Select	c.-43+6292A>G		intron	N/A	NP_001245348.1
	LRRC4C	NM_020929.3		c.-43+6292A>G		intron	N/A	NP_065980.1
	LRRC4C	NR_047673.1		n.991+6292A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	ENST00000528697.6	TSL:1 MANE Select	c.-43+6292A>G		intron	N/A	ENSP00000437132.1
	LRRC4C	ENST00000278198.2	TSL:1	c.-42-18175A>G		intron	N/A	ENSP00000278198.1
	LRRC4C	ENST00000527150.5	TSL:1	c.-43+6292A>G		intron	N/A	ENSP00000436976.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33541 AN: 151840 Hom.: 4525 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.221 AC: 33624 AN: 151958 Hom.: 4549 Cov.: 32 AF XY: 0.218 AC XY: 16179 AN XY: 74268

African (AFR) AF: 0.389 AC: 16100 AN: 41404

American (AMR) AF: 0.213 AC: 3246 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3472

East Asian (EAS) AF: 0.279 AC: 1435 AN: 5146

South Asian (SAS) AF: 0.0841 AC: 405 AN: 4814

European-Finnish (FIN) AF: 0.109 AC: 1153 AN: 10574

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9779 AN: 67960

Other (OTH) AF: 0.216 AC: 456 AN: 2110

Alfa AF: 0.177 Hom.: 8042

Bravo AF: 0.240

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.88
DANN	Benign	0.63
PhyloP100		-2.3
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: rs7936167; hg19: chr11-40156059;