1-69688758-T-C

Variant names:

• chr1-69688758-T-C
• rs1417437
• NM_001370785.2:c.100+10280T>C

Variant summary

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

The NM_001370785.2(LRRC7):​c.100+10280T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 151,882 control chromosomes in the GnomAD database, including 43,475 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 0.75 (43475 hom., cov: 29)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 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.100+10280T>C		intron	N/A	NP_001357714.1
	LRRC7	NM_001366838.3		c.100+10280T>C		intron	N/A	NP_001353767.1
	LRRC7	NM_001330635.3		c.-77+10280T>C		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.100+10280T>C		intron	N/A	ENSP00000498937.2
	LRRC7	ENST00000370958.5	TSL:1	c.100+10280T>C		intron	N/A	ENSP00000359997.1
	LRRC7	ENST00000310961.9	TSL:5	c.-77+10280T>C		intron	N/A	ENSP00000309245.4

Frequencies

GnomAD3 genomes AF: 0.751 AC: 113944 AN: 151764 Hom.: 43440 Cov.: 29

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.751 AC: 114030 AN: 151882 Hom.: 43475 Cov.: 29 AF XY: 0.749 AC XY: 55595 AN XY: 74224

African (AFR) AF: 0.876 AC: 36277 AN: 41420

American (AMR) AF: 0.729 AC: 11124 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2172 AN: 3464

East Asian (EAS) AF: 0.612 AC: 3151 AN: 5150

South Asian (SAS) AF: 0.797 AC: 3836 AN: 4812

European-Finnish (FIN) AF: 0.704 AC: 7395 AN: 10506

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47655 AN: 67954

Other (OTH) AF: 0.737 AC: 1556 AN: 2112

Alfa AF: 0.716 Hom.: 133587

Bravo AF: 0.756

Asia WGS AF: 0.722 AC: 2508 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.83
PhyloP100		-1.2
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: rs1417437; hg19: chr1-70154441;