rs4375425

Variant names:

• chr11-40205830-G-A
• rs4375425
• NM_001258419.2:c.-96+35689C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-40205830-G-A
• chr11-40205830-G-T

Variant summary

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

The NM_001258419.2(LRRC4C):​c.-96+35689C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,962 control chromosomes in the GnomAD database, including 5,587 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 0.25 (5587 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC4C	NM_001258419.2	c.-96+35689C>T		intron_variant	Intron 5 of 6	ENST00000528697.6	NP_001245348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC4C	ENST00000528697.6	c.-96+35689C>T		intron_variant	Intron 5 of 6	1	NM_001258419.2	ENSP00000437132.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37624 AN: 151842 Hom.: 5587 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.352

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.248 AC: 37636 AN: 151962 Hom.: 5587 Cov.: 32 AF XY: 0.248 AC XY: 18384 AN XY: 74260

African (AFR) AF: 0.0913 AC: 3789 AN: 41482

American (AMR) AF: 0.240 AC: 3662 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 921 AN: 3464

East Asian (EAS) AF: 0.333 AC: 1720 AN: 5170

South Asian (SAS) AF: 0.415 AC: 1999 AN: 4820

European-Finnish (FIN) AF: 0.252 AC: 2645 AN: 10514

Middle Eastern (MID) AF: 0.362 AC: 105 AN: 290

European-Non Finnish (NFE) AF: 0.322 AC: 21864 AN: 67932

Other (OTH) AF: 0.295 AC: 624 AN: 2112

Alfa AF: 0.285 Hom.: 1325

Bravo AF: 0.238

Asia WGS AF: 0.371 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.062
DANN	Benign	0.79
PhyloP100		-0.95
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: rs4375425; hg19: chr11-40227380;