1-69890298-A-G

Variant names:

• chr1-69890298-A-G
• rs12037173
• NM_001370785.2:c.648-41209A>G

Variant summary

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

The NM_001370785.2(LRRC7):​c.648-41209A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0485 in 152,328 control chromosomes in the GnomAD database, including 225 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 0.049 (225 hom., cov: 34)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 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.648-41209A>G		intron	N/A	NP_001357714.1
	LRRC7	NM_001366838.3		c.648-41209A>G		intron	N/A	NP_001353767.1
	LRRC7	NM_001330635.3		c.549-41209A>G		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.648-41209A>G		intron	N/A	ENSP00000498937.2
	LRRC7	ENST00000415775.2	TSL:1	c.-872-41209A>G		intron	N/A	ENSP00000394867.2
	LRRC7	ENST00000310961.9	TSL:5	c.549-41209A>G		intron	N/A	ENSP00000309245.4

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7372 AN: 152210 Hom.: 217 Cov.: 34

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0544

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

GnomAD4 genome AF: 0.0485 AC: 7393 AN: 152328 Hom.: 225 Cov.: 34 AF XY: 0.0503 AC XY: 3744 AN XY: 74476

African (AFR) AF: 0.0309 AC: 1285 AN: 41574

American (AMR) AF: 0.0361 AC: 553 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3470

East Asian (EAS) AF: 0.150 AC: 775 AN: 5180

South Asian (SAS) AF: 0.106 AC: 511 AN: 4824

European-Finnish (FIN) AF: 0.0736 AC: 782 AN: 10618

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0467 AC: 3177 AN: 68036

Other (OTH) AF: 0.0643 AC: 136 AN: 2116

Alfa AF: 0.0509 Hom.: 714

Bravo AF: 0.0446

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.3
DANN	Benign	0.52
PhyloP100		0.28
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: rs12037173; hg19: chr1-70355981;