7-100575260-CC-TT

Variant names:

• chr7-100575260-CC-TT
• NM_002319.5:c.1898_1899delGGinsAA
• LRCH4 p.Arg633Gln

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002319.5(LRCH4):​c.1898_1899delGGinsAA​(p.Arg633Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R633W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRCH4 NM_002319.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

Genes affected

LRCH4 (HGNC:6691): (leucine rich repeats and calponin homology domain containing 4) This gene encodes a protein that contains leucine-rich repeats (LRR) at its amino terminus and that is known to be involved in ligand binding. The carboxyl terminus may act as a membrane anchor. Identified structural elements suggest that the encoded protein resembles a receptor. [provided by RefSeq, Jul 2008]

ENSG00000274272 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002319.5. 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
	LRCH4	NM_002319.5	MANE Select	c.1898_1899delGGinsAA	p.Arg633Gln	missense	N/A	NP_002310.2
	LRCH4	NM_001289934.2		c.1854+444_1854+445delGGinsAA		intron	N/A	NP_001276863.1	H7C5D9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRCH4	ENST00000310300.11	TSL:1 MANE Select	c.1898_1899delGGinsAA	p.Arg633Gln	missense	N/A	ENSP00000309689.6	O75427
	LRCH4	ENST00000877649.1		c.1910_1911delGGinsAA	p.Arg637Gln	missense	N/A	ENSP00000547708.1
	LRCH4	ENST00000965051.1		c.1895_1896delGGinsAA	p.Arg632Gln	missense	N/A	ENSP00000635110.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-100172883;