NM_001370785.2:c.4231-2394C>G

Variant names:

• chr1-70073683-C-G
• rs4649909
• NM_001370785.2:c.4231-2394C>G

Variant summary

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

The NM_001370785.2(LRRC7):​c.4231-2394C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 152,298 control chromosomes in the GnomAD database, including 115 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 0.026 (115 hom., cov: 32)
• Consequence: LRRC7 NM_001370785.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0686 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.4231-2394C>G		intron	N/A	NP_001357714.1	A0A494C1A4
	LRRC7	NM_001366838.3		c.4090-2394C>G		intron	N/A	NP_001353767.1
	LRRC7	NM_001330635.3		c.3991-2394C>G		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.4231-2394C>G		intron	N/A	ENSP00000498937.2	A0A494C1A4
	LRRC7	ENST00000310961.9	TSL:5	c.3991-2394C>G		intron	N/A	ENSP00000309245.4	A0A075B6E9
	LRRC7	ENST00000651217.1		n.4147-2394C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3893 AN: 152180 Hom.: 111 Cov.: 32

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00955

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0344

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00764

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0258 AC: 3923 AN: 152298 Hom.: 115 Cov.: 32 AF XY: 0.0252 AC XY: 1877 AN XY: 74482

African (AFR) AF: 0.0708 AC: 2941 AN: 41552

American (AMR) AF: 0.00948 AC: 145 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5190

South Asian (SAS) AF: 0.0344 AC: 166 AN: 4822

European-Finnish (FIN) AF: 0.00650 AC: 69 AN: 10614

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00764 AC: 520 AN: 68028

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.0179 Hom.: 14

Bravo AF: 0.0278

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		-0.032
Mutation Taster		=100/0	polymorphism (auto)

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: rs4649909; hg19: chr1-70539366;