1-69782432-T-C

Variant names:

• chr1-69782432-T-C
• rs7520521
• NM_001370785.2:c.304-9611T>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.304-9611T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,018 control chromosomes in the GnomAD database, including 17,811 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 (17811 hom., cov: 31)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 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.304-9611T>C		intron	N/A	NP_001357714.1	A0A494C1A4
	LRRC7	NM_001366838.3		c.304-9611T>C		intron	N/A	NP_001353767.1
	LRRC7	NM_001330635.3		c.205-9611T>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.304-9611T>C		intron	N/A	ENSP00000498937.2	A0A494C1A4
	LRRC7	ENST00000370958.5	TSL:1	c.304-9611T>C		intron	N/A	ENSP00000359997.1	B1AKT2
	LRRC7	ENST00000310961.9	TSL:5	c.205-9611T>C		intron	N/A	ENSP00000309245.4	A0A075B6E9

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72011 AN: 151900 Hom.: 17770 Cov.: 31

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.474 AC: 72109 AN: 152018 Hom.: 17811 Cov.: 31 AF XY: 0.472 AC XY: 35077 AN XY: 74288

African (AFR) AF: 0.611 AC: 25310 AN: 41438

American (AMR) AF: 0.475 AC: 7257 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1481 AN: 3472

East Asian (EAS) AF: 0.588 AC: 3039 AN: 5166

South Asian (SAS) AF: 0.393 AC: 1896 AN: 4824

European-Finnish (FIN) AF: 0.383 AC: 4046 AN: 10564

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27517 AN: 67970

Other (OTH) AF: 0.476 AC: 1002 AN: 2104

Alfa AF: 0.434 Hom.: 49652

Bravo AF: 0.486

Asia WGS AF: 0.533 AC: 1853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.24
DANN	Benign	0.82
PhyloP100		-1.8
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: rs7520521; hg19: chr1-70248115;