1-69713675-G-T

Variant names:

• chr1-69713675-G-T
• rs1796969
• NM_001370785.2:c.100+35197G>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.100+35197G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 151,084 control chromosomes in the GnomAD database, including 34,628 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 0.67 (34628 hom., cov: 28)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.791 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC7	NM_001370785.2	MANE Select	c.100+35197G>T		intron	N/A	NP_001357714.1	A0A494C1A4
	LRRC7	NM_001366838.3		c.100+35197G>T		intron	N/A	NP_001353767.1
	LRRC7	NM_001330635.3		c.-76-2467G>T		intron	N/A	NP_001317564.1	A0A075B6E9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC7	ENST00000651989.2	MANE Select	c.100+35197G>T		intron	N/A	ENSP00000498937.2	A0A494C1A4
	LRRC7	ENST00000370958.5	TSL:1	c.100+35197G>T		intron	N/A	ENSP00000359997.1	B1AKT2
	LRRC7	ENST00000310961.9	TSL:5	c.-76-2467G>T		intron	N/A	ENSP00000309245.4	A0A075B6E9

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101246 AN: 150966 Hom.: 34582 Cov.: 28

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.671 AC: 101349 AN: 151084 Hom.: 34628 Cov.: 28 AF XY: 0.671 AC XY: 49483 AN XY: 73708

African (AFR) AF: 0.798 AC: 32827 AN: 41132

American (AMR) AF: 0.673 AC: 10158 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1555 AN: 3462

East Asian (EAS) AF: 0.595 AC: 3060 AN: 5140

South Asian (SAS) AF: 0.716 AC: 3423 AN: 4780

European-Finnish (FIN) AF: 0.621 AC: 6452 AN: 10386

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.616 AC: 41789 AN: 67790

Other (OTH) AF: 0.657 AC: 1375 AN: 2092

Alfa AF: 0.671 Hom.: 6779

Bravo AF: 0.679

Asia WGS AF: 0.682 AC: 2367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.30
DANN	Benign	0.67
PhyloP100		-0.45
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: rs1796969; hg19: chr1-70179358;