1-69813923-C-T

Variant names:

• chr1-69813923-C-T
• rs1913269
• NM_001370785.2:c.422-11825C>T

Variant summary

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

The NM_001370785.2(LRRC7):​c.422-11825C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,910 control chromosomes in the GnomAD database, including 31,001 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 0.64 (31001 hom., cov: 32)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370785.2. 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.422-11825C>T		intron	N/A	NP_001357714.1
	LRRC7	NM_001366838.3		c.422-11825C>T		intron	N/A	NP_001353767.1
	LRRC7	NM_001330635.3		c.323-11825C>T		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.422-11825C>T		intron	N/A	ENSP00000498937.2
	LRRC7	ENST00000370958.5	TSL:1	c.422-11825C>T		intron	N/A	ENSP00000359997.1
	LRRC7	ENST00000310961.9	TSL:5	c.323-11825C>T		intron	N/A	ENSP00000309245.4

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96561 AN: 151792 Hom.: 30969 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.636 AC: 96647 AN: 151910 Hom.: 31001 Cov.: 32 AF XY: 0.635 AC XY: 47098 AN XY: 74208

African (AFR) AF: 0.609 AC: 25220 AN: 41442

American (AMR) AF: 0.672 AC: 10217 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2215 AN: 3468

East Asian (EAS) AF: 0.783 AC: 4060 AN: 5186

South Asian (SAS) AF: 0.549 AC: 2648 AN: 4826

European-Finnish (FIN) AF: 0.646 AC: 6802 AN: 10522

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43102 AN: 67946

Other (OTH) AF: 0.676 AC: 1422 AN: 2104

Alfa AF: 0.624 Hom.: 5242

Bravo AF: 0.643

Asia WGS AF: 0.687 AC: 2386 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.20
PhyloP100		-0.12
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: rs1913269; hg19: chr1-70279606;