NM_001370785.2:c.2+49094C>G

Variant names:

• chr1-69617735-C-G
• rs1773339
• NM_001370785.2:c.2+49094C>G

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+49094C>G 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 151,694 control chromosomes in the GnomAD database, including 1,576 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 (1576 hom., cov: 30)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.2+49094C>G		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+49094C>G		intron_variant	Intron 1 of 26		NM_001370785.2	ENSP00000498937.2
LRRC7	ENST00000370958.5	c.2+49094C>G		intron_variant	Intron 1 of 7	1		ENSP00000359997.1
LRRC7	ENST00000310961.9	c.-175+49094C>G		intron_variant	Intron 1 of 26	5		ENSP00000309245.4

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19370 AN: 151578 Hom.: 1575 Cov.: 30

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.128 AC: 19374 AN: 151694 Hom.: 1576 Cov.: 30 AF XY: 0.127 AC XY: 9386 AN XY: 74112

African (AFR) AF: 0.0433 AC: 1794 AN: 41442

American (AMR) AF: 0.178 AC: 2702 AN: 15174

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

East Asian (EAS) AF: 0.0172 AC: 88 AN: 5124

South Asian (SAS) AF: 0.186 AC: 895 AN: 4802

European-Finnish (FIN) AF: 0.140 AC: 1469 AN: 10526

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

European-Non Finnish (NFE) AF: 0.172 AC: 11666 AN: 67850

Other (OTH) AF: 0.123 AC: 258 AN: 2102

Alfa AF: 0.0879 Hom.: 127

Bravo AF: 0.126

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.64
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: rs1773339; hg19: chr1-70083418;