1-69782432-T-C

Position:

• chr1-69782432-T-C

Variant summary

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

The NM_001370785.2(LRRC7):​c.304-9611T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,018 control chromosomes in the GnomAD database, including 17,811 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 0.47 (17811 hom., cov: 31)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.304-9611T>C		intron_variant		ENST00000651989.2	NP_001357714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC7	ENST00000651989.2	c.304-9611T>C		intron_variant			NM_001370785.2	ENSP00000498937	P1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72011 AN: 151900 Hom.: 17770 Cov.: 31

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.474 AC: 72109 AN: 152018 Hom.: 17811 Cov.: 31 AF XY: 0.472 AC XY: 35077 AN XY: 74288

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.476

Alfa AF: 0.424 Hom.: 29806

Bravo AF: 0.486

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.82

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: rs7520521; hg19: chr1-70248115;