1-70028224-T-G

Position:

• chr1-70028224-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370785.2(LRRC7):​c.1848T>G​(p.Asn616Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC7 NM_001370785.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.821

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-AS1 (HGNC:40843): (LRRC7 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC7	NM_001370785.2	c.1848T>G	p.Asn616Lys	missense_variant	18/27	ENST00000651989.2	NP_001357714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC7	ENST00000651989.2	c.1848T>G	p.Asn616Lys	missense_variant	18/27		NM_001370785.2	ENSP00000498937.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 24, 2024

The c.1734T>G (p.N578K) alteration is located in exon 16 (coding exon 16) of the LRRC7 gene. This alteration results from a T to G substitution at nucleotide position 1734, causing the asparagine (N) at amino acid position 578 to be replaced by a lysine (K). 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	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T
Eigen	Benign	0.19
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.044	.;D
Polyphen		1.0	.;D
Vest4		0.92
MutPred		0.37		.;Loss of sheet (P = 0.0181);
MVP		0.49
MPC		0.90
ClinPred		0.95	D
GERP RS		3.6
Varity_R		0.33
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-70493907;