NM_001370785.2:c.2+44304G>A

Variant names:

• chr1-69612945-G-A
• rs1749499
• NM_001370785.2:c.2+44304G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370785.2(LRRC7):​c.2+44304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 151,906 control chromosomes in the GnomAD database, including 1,601 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 0.13 (1601 hom., cov: 32)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.2+44304G>A		intron_variant	Intron 1 of 26	ENST00000651989.2	NP_001357714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC7	ENST00000651989.2	c.2+44304G>A		intron_variant	Intron 1 of 26		NM_001370785.2	ENSP00000498937.2
LRRC7	ENST00000370958.5	c.2+44304G>A		intron_variant	Intron 1 of 7	1		ENSP00000359997.1
LRRC7	ENST00000310961.9	c.-175+44304G>A		intron_variant	Intron 1 of 26	5		ENSP00000309245.4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19521 AN: 151786 Hom.: 1599 Cov.: 32

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.129 AC: 19533 AN: 151906 Hom.: 1601 Cov.: 32 AF XY: 0.128 AC XY: 9483 AN XY: 74236

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.127

Alfa AF: 0.160 Hom.: 344

Bravo AF: 0.126

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1749499; hg19: chr1-70078628;