1-69869999-T-C

Variant names:

• chr1-69869999-T-C
• rs2226284
• NM_001370785.2:c.647+31716T>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.647+31716T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,900 control chromosomes in the GnomAD database, including 16,823 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 0.47 (16823 hom., cov: 32)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• Publications: 15 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 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.647+31716T>C		intron	N/A	NP_001357714.1	A0A494C1A4
	LRRC7	NM_001366838.3		c.647+31716T>C		intron	N/A	NP_001353767.1
	LRRC7	NM_001330635.3		c.548+31716T>C		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.647+31716T>C		intron	N/A	ENSP00000498937.2	A0A494C1A4
	LRRC7	ENST00000370958.5	TSL:1	c.648-3468T>C		intron	N/A	ENSP00000359997.1	B1AKT2
	LRRC7	ENST00000310961.9	TSL:5	c.548+31716T>C		intron	N/A	ENSP00000309245.4	A0A075B6E9

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70841 AN: 151784 Hom.: 16800 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.467 AC: 70894 AN: 151900 Hom.: 16823 Cov.: 32 AF XY: 0.464 AC XY: 34429 AN XY: 74244

African (AFR) AF: 0.396 AC: 16405 AN: 41410

American (AMR) AF: 0.507 AC: 7730 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1878 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2849 AN: 5162

South Asian (SAS) AF: 0.363 AC: 1748 AN: 4816

European-Finnish (FIN) AF: 0.464 AC: 4902 AN: 10562

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33553 AN: 67924

Other (OTH) AF: 0.473 AC: 998 AN: 2110

Alfa AF: 0.485 Hom.: 56347

Bravo AF: 0.471

Asia WGS AF: 0.424 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.79
PhyloP100		-0.55
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: rs2226284; hg19: chr1-70335682;