NM_001370785.2:c.4620+5109G>A

Variant names:

• chr1-70112935-G-A
• rs7521532
• NM_001370785.2:c.4620+5109G>A

Variant summary

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

The NM_001370785.2(LRRC7):​c.4620+5109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,048 control chromosomes in the GnomAD database, including 1,736 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 0.13 (1736 hom., cov: 32)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.4620+5109G>A		intron_variant	Intron 26 of 26	ENST00000651989.2	NP_001357714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC7	ENST00000651989.2	c.4620+5109G>A		intron_variant	Intron 26 of 26		NM_001370785.2	ENSP00000498937.2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19450 AN: 151930 Hom.: 1722 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0937

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.128 AC: 19507 AN: 152048 Hom.: 1736 Cov.: 32 AF XY: 0.128 AC XY: 9486 AN XY: 74362

African (AFR) AF: 0.247 AC: 10224 AN: 41422

American (AMR) AF: 0.0937 AC: 1431 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3464

East Asian (EAS) AF: 0.138 AC: 712 AN: 5172

South Asian (SAS) AF: 0.215 AC: 1037 AN: 4816

European-Finnish (FIN) AF: 0.0270 AC: 286 AN: 10590

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0739 AC: 5023 AN: 67996

Other (OTH) AF: 0.122 AC: 257 AN: 2106

Alfa AF: 0.0979 Hom.: 533

Bravo AF: 0.138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.70
PhyloP100		-0.25
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: rs7521532; hg19: chr1-70578618;