chr1-70049250-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 842 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.4111-3776G>T		intron_variant	Intron 22 of 26	ENST00000651989.2	NP_001357714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC7	ENST00000651989.2	c.4111-3776G>T		intron_variant	Intron 22 of 26		NM_001370785.2	ENSP00000498937.2
LRRC7	ENST00000415775.2	c.1849-3776G>T		intron_variant	Intron 16 of 20	1		ENSP00000394867.2
LRRC7	ENST00000310961.9	c.3871-3776G>T		intron_variant	Intron 22 of 26	5		ENSP00000309245.4
LRRC7	ENST00000651217.1	n.4027-3776G>T		intron_variant	Intron 20 of 24

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

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.00641

Gnomad4 NFE AF: 0.00731

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.00529 Hom.: 4

Bravo AF: 0.00451

Asia WGS AF: 0.0170 AC: 59 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1009127; hg19: chr1-70514933;