1-70073683-C-G

Position:

• chr1-70073683-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370785.2(LRRC7):​c.4231-2394C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 152,298 control chromosomes in the GnomAD database, including 115 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 0.026 (115 hom., cov: 32)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC7	NM_001370785.2	c.4231-2394C>G		intron_variant		ENST00000651989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC7	ENST00000651989.2	c.4231-2394C>G		intron_variant			NM_001370785.2	P1
LRRC7	ENST00000415775.2	c.1969-2394C>G		intron_variant		1
LRRC7	ENST00000310961.9	c.3991-2394C>G		intron_variant		5
LRRC7	ENST00000651217.1	n.4147-2394C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3893 AN: 152180 Hom.: 111 Cov.: 32

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00955

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00764

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0258 AC: 3923 AN: 152298 Hom.: 115 Cov.: 32 AF XY: 0.0252 AC XY: 1877 AN XY: 74482

Gnomad4 AFR AF: 0.0708

Gnomad4 AMR AF: 0.00948

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.00650

Gnomad4 NFE AF: 0.00764

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0179 Hom.: 14

Bravo AF: 0.0278

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs4649909; hg19: chr1-70539366;