1-69938857-A-T

Variant names:

• chr1-69938857-A-T
• rs1023008
• NM_001370785.2:c.711+7287A>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.711+7287A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 150,936 control chromosomes in the GnomAD database, including 23,302 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 0.55 (23302 hom., cov: 28)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• 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 (EAS) allele frequency at 95% confidence interval = 0.684 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.711+7287A>T		intron	N/A	NP_001357714.1	A0A494C1A4
	LRRC7	NM_001366838.3		c.711+7287A>T		intron	N/A	NP_001353767.1
	LRRC7	NM_001330635.3		c.612+7287A>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.711+7287A>T		intron	N/A	ENSP00000498937.2	A0A494C1A4
	LRRC7	ENST00000310961.9	TSL:5	c.612+7287A>T		intron	N/A	ENSP00000309245.4	A0A075B6E9
	LRRC7	ENST00000651217.1		n.627+7287A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.555 AC: 83651 AN: 150824 Hom.: 23266 Cov.: 28

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.555 AC: 83726 AN: 150936 Hom.: 23302 Cov.: 28 AF XY: 0.552 AC XY: 40640 AN XY: 73682

African (AFR) AF: 0.560 AC: 23044 AN: 41136

American (AMR) AF: 0.557 AC: 8450 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2014 AN: 3464

East Asian (EAS) AF: 0.703 AC: 3599 AN: 5122

South Asian (SAS) AF: 0.480 AC: 2301 AN: 4796

European-Finnish (FIN) AF: 0.535 AC: 5531 AN: 10332

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36743 AN: 67634

Other (OTH) AF: 0.573 AC: 1201 AN: 2096

Alfa AF: 0.530 Hom.: 2578

Bravo AF: 0.561

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.8
DANN	Benign	0.37
PhyloP100		1.4
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: rs1023008; hg19: chr1-70404540;