chr1-69986354-C-T

Position:

• chr1-69986354-C-T

Variant summary

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

The NM_001370785.2(LRRC7):​c.899C>T​(p.Ser300Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRRC7 NM_001370785.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.35

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 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	UniProt
LRRC7	NM_001370785.2	c.899C>T	p.Ser300Phe	missense_variant	10/27	ENST00000651989.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC7	ENST00000651989.2	c.899C>T	p.Ser300Phe	missense_variant	10/27		NM_001370785.2	P1
LRRC7	ENST00000415775.2	c.-621C>T		5_prime_UTR_variant	8/21	1
LRRC7	ENST00000310961.9	c.800C>T	p.Ser267Phe	missense_variant	11/27	5
LRRC7	ENST00000651217.1	n.815C>T		non_coding_transcript_exon_variant	8/25

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460868 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726752

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

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

Dec 27, 2022

The c.785C>T (p.S262F) alteration is located in exon 8 (coding exon 8) of the LRRC7 gene. This alteration results from a C to T substitution at nucleotide position 785, causing the serine (S) at amino acid position 262 to be replaced by a phenylalanine (F). 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	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.98	.;L
MutationTaster	Benign	0.95	D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.023	D;D
Sift4G	Pathogenic	0.0010	.;D
Polyphen		0.98	.;D
Vest4		0.75
MutPred		0.56		.;Loss of disorder (P = 0.0075);
MVP		0.71
MPC		2.2
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.52
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr1-70452037;