1-70011852-T-G

Position:

• chr1-70011852-T-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2 BP4_Moderate

The NM_001370785.2(LRRC7):​c.1060T>G​(p.Ser354Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,434,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: LRRC7 NM_001370785.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

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 Likely_benign. Variant got -1 ACMG points.

• PP2: Missense variant where missense usually causes diseases, LRRC7
• BP4: Computational evidence support a benign effect (MetaRNN=0.10977143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC7	NM_001370785.2	c.1060T>G	p.Ser354Ala	missense_variant	12/27	ENST00000651989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC7	ENST00000651989.2	c.1060T>G	p.Ser354Ala	missense_variant	12/27		NM_001370785.2	P1
LRRC7	ENST00000415775.2	c.-460T>G		5_prime_UTR_variant	10/21	1
LRRC7	ENST00000310961.9	c.961T>G	p.Ser321Ala	missense_variant	13/27	5
LRRC7	ENST00000651217.1	n.976T>G		non_coding_transcript_exon_variant	10/25

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000279 AC: 4 AN: 1434644 Hom.: 0 Cov.: 26 AF XY: 0.00000140 AC XY: 1 AN XY: 715504

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.19e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2023

The c.946T>G (p.S316A) alteration is located in exon 10 (coding exon 10) of the LRRC7 gene. This alteration results from a T to G substitution at nucleotide position 946, causing the serine (S) at amino acid position 316 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.036
Sift	Benign	0.27	T;T
Polyphen		0.0	.;B
Vest4		0.15
MutPred		0.29		.;Loss of glycosylation at S316 (P = 0.0207);
MVP		0.51
MPC		1.0
ClinPred		0.13	T
GERP RS		1.2
Varity_R		0.056
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1656539329; hg19: chr1-70477535;