11-40530738-A-T

Variant names:

• chr11-40530738-A-T
• rs16934907
• NM_001258419.2:c.-270+117404T>A

Variant summary

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

The NM_001258419.2(LRRC4C):​c.-270+117404T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0878 in 152,172 control chromosomes in the GnomAD database, including 1,664 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 0.088 (1664 hom., cov: 32)
• Consequence: LRRC4C NM_001258419.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 0 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 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.-270+117404T>A		intron	N/A	NP_001245348.1
	LRRC4C	NM_020929.3		c.-190+117404T>A		intron	N/A	NP_065980.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC4C	ENST00000528697.6	TSL:1 MANE Select	c.-270+117404T>A		intron	N/A	ENSP00000437132.1
	LRRC4C	ENST00000530763.5	TSL:1	c.-190+117404T>A		intron	N/A	ENSP00000434761.1

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13321 AN: 152054 Hom.: 1656 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0602

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.0246

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.00395

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00773

Gnomad OTH AF: 0.0675

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

GnomAD4 genome AF: 0.0878 AC: 13367 AN: 152172 Hom.: 1664 Cov.: 32 AF XY: 0.0836 AC XY: 6224 AN XY: 74410

African (AFR) AF: 0.278 AC: 11546 AN: 41468

American (AMR) AF: 0.0602 AC: 919 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3472

East Asian (EAS) AF: 0.0243 AC: 126 AN: 5186

South Asian (SAS) AF: 0.00435 AC: 21 AN: 4830

European-Finnish (FIN) AF: 0.00395 AC: 42 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00774 AC: 526 AN: 68000

Other (OTH) AF: 0.0668 AC: 141 AN: 2112

Alfa AF: 0.0554 Hom.: 122

Bravo AF: 0.100

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.79
PhyloP100		0.61
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: rs16934907; hg19: chr11-40552288;