1-69650073-A-T

Position:

• chr1-69650073-A-T

Variant summary

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

The NM_001370785.2(LRRC7):​c.3-28308A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,150 control chromosomes in the GnomAD database, including 1,555 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 (1555 hom., cov: 31)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

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=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.3-28308A>T		intron_variant		ENST00000651989.2	NP_001357714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC7	ENST00000651989.2	c.3-28308A>T		intron_variant			NM_001370785.2	ENSP00000498937.2
LRRC7	ENST00000370958.5	c.3-28308A>T		intron_variant		1		ENSP00000359997.1
LRRC7	ENST00000310961.9	c.-174-28308A>T		intron_variant		5		ENSP00000309245.4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19230 AN: 152032 Hom.: 1554 Cov.: 31

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0176

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.126 AC: 19227 AN: 152150 Hom.: 1555 Cov.: 31 AF XY: 0.125 AC XY: 9314 AN XY: 74394

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0788 Hom.: 109

Bravo AF: 0.124

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.5
DANN	Benign	0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1245072; hg19: chr1-70115756;