rs12037173

Positions:

• chr1-69890298-A-G
• chr1-69890298-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.648-41209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0485 in 152,328 control chromosomes in the GnomAD database, including 225 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 0.049 (225 hom., cov: 34)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.648-41209A>G		intron_variant		ENST00000651989.2	NP_001357714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC7	ENST00000651989.2	c.648-41209A>G		intron_variant			NM_001370785.2	ENSP00000498937	P1
LRRC7	ENST00000415775.2	c.-872-41209A>G		intron_variant		1		ENSP00000394867
LRRC7	ENST00000310961.9	c.549-41209A>G		intron_variant		5		ENSP00000309245
LRRC7	ENST00000651217.1	n.564-41209A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7372 AN: 152210 Hom.: 217 Cov.: 34

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0544

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

GnomAD4 genome AF: 0.0485 AC: 7393 AN: 152328 Hom.: 225 Cov.: 34 AF XY: 0.0503 AC XY: 3744 AN XY: 74476

Gnomad4 AFR AF: 0.0309

Gnomad4 AMR AF: 0.0361

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0736

Gnomad4 NFE AF: 0.0467

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0536 Hom.: 332

Bravo AF: 0.0446

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.3
DANN	Benign	0.52

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: rs12037173; hg19: chr1-70355981;