1-69582381-C-T

Variant names:

• chr1-69582381-C-T
• rs1245058
• NM_001370785.2:c.2+13740C>T

Variant summary

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

The NM_001370785.2(LRRC7):​c.2+13740C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,140 control chromosomes in the GnomAD database, including 1,909 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 0.15 (1909 hom., cov: 32)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961
• Publications: 2 publications found

Genes affected

LRRC7 (HGNC:18531): (leucine rich repeat containing 7) Predicted to be involved in several processes, including establishment or maintenance of epithelial cell apical/basal polarity; positive regulation of neuron projection development; and receptor clustering. Located in several cellular components, including centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRRC7 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.2+13740C>T		intron_variant	Intron 1 of 26	ENST00000651989.2	NP_001357714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC7	ENST00000651989.2	c.2+13740C>T		intron_variant	Intron 1 of 26		NM_001370785.2	ENSP00000498937.2
LRRC7	ENST00000370958.5	c.2+13740C>T		intron_variant	Intron 1 of 7	1		ENSP00000359997.1
LRRC7	ENST00000310961.9	c.-175+13740C>T		intron_variant	Intron 1 of 26	5		ENSP00000309245.4

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22960 AN: 152024 Hom.: 1906 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.151 AC: 22970 AN: 152140 Hom.: 1909 Cov.: 32 AF XY: 0.149 AC XY: 11111 AN XY: 74374

African (AFR) AF: 0.117 AC: 4843 AN: 41512

American (AMR) AF: 0.189 AC: 2887 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 352 AN: 3468

East Asian (EAS) AF: 0.0176 AC: 91 AN: 5172

South Asian (SAS) AF: 0.186 AC: 895 AN: 4820

European-Finnish (FIN) AF: 0.147 AC: 1552 AN: 10588

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11882 AN: 67986

Other (OTH) AF: 0.137 AC: 289 AN: 2108

Alfa AF: 0.0978 Hom.: 152

Bravo AF: 0.151

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.45
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1245058; hg19: chr1-70048064;