1-70101505-C-G

Variant names:

• chr1-70101505-C-G
• rs672961
• NM_001370785.2:c.4546-6247C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000651989.2(LRRC7):​c.4546-6247C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 152,296 control chromosomes in the GnomAD database, including 74,454 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 0.99 (74454 hom., cov: 31)
• Consequence: LRRC7 ENST00000651989.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• 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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000651989.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC7	NM_001370785.2	MANE Select	c.4546-6247C>G		intron	N/A	NP_001357714.1
	LRRC7	NM_001366838.3		c.4405-6247C>G		intron	N/A	NP_001353767.1
	LRRC7	NM_001330635.3		c.4306-6247C>G		intron	N/A	NP_001317564.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC7	ENST00000651989.2	MANE Select	c.4546-6247C>G		intron	N/A	ENSP00000498937.2
	LRRC7	ENST00000415775.2	TSL:1	c.2284-6247C>G		intron	N/A	ENSP00000394867.2
	LRRC7	ENST00000310961.9	TSL:5	c.4306-6247C>G		intron	N/A	ENSP00000309245.4

Frequencies

GnomAD3 genomes AF: 0.988 AC: 150402 AN: 152178 Hom.: 74390 Cov.: 31

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.989

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.990

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

GnomAD4 genome AF: 0.988 AC: 150525 AN: 152296 Hom.: 74454 Cov.: 31 AF XY: 0.987 AC XY: 73527 AN XY: 74466

African (AFR) AF: 0.998 AC: 41476 AN: 41578

American (AMR) AF: 0.997 AC: 15241 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3470 AN: 3472

East Asian (EAS) AF: 0.832 AC: 4289 AN: 5158

South Asian (SAS) AF: 0.990 AC: 4778 AN: 4826

European-Finnish (FIN) AF: 0.989 AC: 10497 AN: 10616

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67472 AN: 68034

Other (OTH) AF: 0.991 AC: 2097 AN: 2116

Alfa AF: 0.992 Hom.: 4044

Bravo AF: 0.988

Asia WGS AF: 0.933 AC: 3244 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.75
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs672961; hg19: chr1-70567188;