chr1-69760490-T-C

Position:

• chr1-69760490-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001370785.2(LRRC7):​c.303+97T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0285 in 978,586 control chromosomes in the GnomAD database, including 491 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 0.031 (78 hom., cov: 32)
  • Exomes 𝑓: 0.028 (413 hom.)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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]

LOC124904199 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0307 (4673/152136) while in subpopulation AFR AF= 0.046 (1912/41534). AF 95% confidence interval is 0.0443. There are 78 homozygotes in gnomad4. There are 2239 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4673 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.303+97T>C		intron_variant		ENST00000651989.2	NP_001357714.1
LOC124904199	XR_007066167.1	n.264+55A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC7	ENST00000651989.2	c.303+97T>C		intron_variant			NM_001370785.2	ENSP00000498937	P1

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4678 AN: 152018 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.0226

Gnomad SAS AF: 0.0364

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.0280 AC: 23179 AN: 826450 Hom.: 413 AF XY: 0.0284 AC XY: 12071 AN XY: 424584

Gnomad4 AFR exome AF: 0.0473

Gnomad4 AMR exome AF: 0.00876

Gnomad4 ASJ exome AF: 0.0177

Gnomad4 EAS exome AF: 0.0231

Gnomad4 SAS exome AF: 0.0362

Gnomad4 FIN exome AF: 0.0148

Gnomad4 NFE exome AF: 0.0294

Gnomad4 OTH exome AF: 0.0260

GnomAD4 genome AF: 0.0307 AC: 4673 AN: 152136 Hom.: 78 Cov.: 32 AF XY: 0.0301 AC XY: 2239 AN XY: 74394

Gnomad4 AFR AF: 0.0460

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.0364

Gnomad4 FIN AF: 0.0146

Gnomad4 NFE AF: 0.0292

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0319 Hom.: 21

Bravo AF: 0.0299

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	13
DANN	Benign	0.80

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: rs17325887; hg19: chr1-70226173;