NM_001370785.2:c.3-26280G>C

Variant names:

• chr1-69652101-G-C
• rs227108
• NM_001370785.2:c.3-26280G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370785.2(LRRC7):​c.3-26280G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,116 control chromosomes in the GnomAD database, including 2,099 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 0.16 (2099 hom., cov: 31)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 0 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 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.3-26280G>C		intron	N/A	NP_001357714.1	A0A494C1A4
	LRRC7	NM_001366838.3		c.3-26280G>C		intron	N/A	NP_001353767.1
	LRRC7	NM_001330635.3		c.-174-26280G>C		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.3-26280G>C		intron	N/A	ENSP00000498937.2	A0A494C1A4
	LRRC7	ENST00000370958.5	TSL:1	c.3-26280G>C		intron	N/A	ENSP00000359997.1	B1AKT2
	LRRC7	ENST00000310961.9	TSL:5	c.-174-26280G>C		intron	N/A	ENSP00000309245.4	A0A075B6E9

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24396 AN: 151998 Hom.: 2095 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0333

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.160 AC: 24403 AN: 152116 Hom.: 2099 Cov.: 31 AF XY: 0.159 AC XY: 11855 AN XY: 74356

African (AFR) AF: 0.146 AC: 6054 AN: 41502

American (AMR) AF: 0.198 AC: 3024 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3468

East Asian (EAS) AF: 0.0330 AC: 171 AN: 5178

South Asian (SAS) AF: 0.197 AC: 950 AN: 4820

European-Finnish (FIN) AF: 0.134 AC: 1423 AN: 10586

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11930 AN: 67984

Other (OTH) AF: 0.147 AC: 309 AN: 2108

Alfa AF: 0.171 Hom.: 292

Bravo AF: 0.162

Asia WGS AF: 0.110 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.56
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs227108; hg19: chr1-70117784;