NM_001370785.2:c.4111-3776G>T

Variant names:

• chr1-70049250-G-T
• rs1009127
• NM_001370785.2:c.4111-3776G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001370785.2(LRRC7):​c.4111-3776G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00553 in 152,190 control chromosomes in the GnomAD database, including 6 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 0.0055 (6 hom., cov: 32)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 1 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=-0.91).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00553 (842/152190) while in subpopulation SAS AF = 0.0346 (167/4824). AF 95% confidence interval is 0.0303. There are 6 homozygotes in GnomAd4. There are 429 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 842 AD gene.

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.4111-3776G>T		intron	N/A	NP_001357714.1
	LRRC7	NM_001366838.3		c.3970-3776G>T		intron	N/A	NP_001353767.1
	LRRC7	NM_001330635.3		c.3871-3776G>T		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.4111-3776G>T		intron	N/A	ENSP00000498937.2
	LRRC7	ENST00000310961.9	TSL:5	c.3871-3776G>T		intron	N/A	ENSP00000309245.4
	LRRC7	ENST00000651217.1		n.4027-3776G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00554 AC: 842 AN: 152072 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00731

Gnomad OTH AF: 0.00384

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

GnomAD4 genome AF: 0.00553 AC: 842 AN: 152190 Hom.: 6 Cov.: 32 AF XY: 0.00576 AC XY: 429 AN XY: 74432

African (AFR) AF: 0.00106 AC: 44 AN: 41538

American (AMR) AF: 0.00144 AC: 22 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00721 AC: 25 AN: 3466

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4824

European-Finnish (FIN) AF: 0.00641 AC: 68 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00731 AC: 497 AN: 67994

Other (OTH) AF: 0.00380 AC: 8 AN: 2106

Alfa AF: 0.00533 Hom.: 5

Bravo AF: 0.00451

Asia WGS AF: 0.0170 AC: 59 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		-0.018

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: rs1009127; hg19: chr1-70514933;