rs1749499

Variant names:

• chr1-69612945-G-A
• rs1749499
• NM_001370785.2:c.2+44304G>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.2+44304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 151,906 control chromosomes in the GnomAD database, including 1,601 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 (1601 hom., cov: 32)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.2+44304G>A		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+44304G>A		intron_variant	Intron 1 of 26		NM_001370785.2	ENSP00000498937.2
LRRC7	ENST00000370958.5	c.2+44304G>A		intron_variant	Intron 1 of 7	1		ENSP00000359997.1
LRRC7	ENST00000310961.9	c.-175+44304G>A		intron_variant	Intron 1 of 26	5		ENSP00000309245.4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19521 AN: 151786 Hom.: 1599 Cov.: 32

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.129 AC: 19533 AN: 151906 Hom.: 1601 Cov.: 32 AF XY: 0.128 AC XY: 9483 AN XY: 74236

African (AFR) AF: 0.0438 AC: 1813 AN: 41438

American (AMR) AF: 0.180 AC: 2734 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 316 AN: 3468

East Asian (EAS) AF: 0.0176 AC: 91 AN: 5156

South Asian (SAS) AF: 0.189 AC: 909 AN: 4816

European-Finnish (FIN) AF: 0.142 AC: 1497 AN: 10570

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11719 AN: 67926

Other (OTH) AF: 0.127 AC: 268 AN: 2102

Alfa AF: 0.156 Hom.: 347

Bravo AF: 0.126

Asia WGS AF: 0.106 AC: 368 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	6.2
DANN	Benign	0.56
PhyloP100		0.64
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: rs1749499; hg19: chr1-70078628;