chr1-69640464-G-A

Variant names:

• chr1-69640464-G-A
• rs800923
• NM_001370785.2:c.3-37917G>A

Variant summary

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

The NM_001370785.2(LRRC7):​c.3-37917G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 151,314 control chromosomes in the GnomAD database, including 41,050 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 0.73 (41050 hom., cov: 31)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 0 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.3-37917G>A		intron_variant	Intron 1 of 26	ENST00000651989.2	NP_001357714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC7	ENST00000651989.2	c.3-37917G>A		intron_variant	Intron 1 of 26		NM_001370785.2	ENSP00000498937.2
LRRC7	ENST00000370958.5	c.3-37917G>A		intron_variant	Intron 1 of 7	1		ENSP00000359997.1
LRRC7	ENST00000310961.9	c.-174-37917G>A		intron_variant	Intron 1 of 26	5		ENSP00000309245.4

Frequencies

GnomAD3 genomes AF: 0.734 AC: 110916 AN: 151204 Hom.: 41022 Cov.: 31

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.673

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.734 AC: 110996 AN: 151314 Hom.: 41050 Cov.: 31 AF XY: 0.734 AC XY: 54216 AN XY: 73874

African (AFR) AF: 0.815 AC: 33766 AN: 41412

American (AMR) AF: 0.758 AC: 11472 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2024 AN: 3454

East Asian (EAS) AF: 0.639 AC: 3276 AN: 5128

South Asian (SAS) AF: 0.797 AC: 3841 AN: 4820

European-Finnish (FIN) AF: 0.694 AC: 7287 AN: 10498

Middle Eastern (MID) AF: 0.667 AC: 184 AN: 276

European-Non Finnish (NFE) AF: 0.696 AC: 47043 AN: 67580

Other (OTH) AF: 0.716 AC: 1498 AN: 2092

Alfa AF: 0.736 Hom.: 5373

Bravo AF: 0.740

Asia WGS AF: 0.734 AC: 2535 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.40
PhyloP100		0.079
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs800923; hg19: chr1-70106147;