18-62187945-T-G

Variant names:

• chr18-62187945-T-G
• rs761718974
• NM_001346231.2:c.440T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001346231.2(RELCH):​c.440T>G​(p.Met147Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M147T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RELCH NM_001346231.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 0 publications found

Genes affected

RELCH (HGNC:29289): (RAB11 binding and LisH domain, coiled-coil and HEAT repeat containing) Involved in intracellular cholesterol transport. Located in recycling endosome and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040603966).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346231.2. 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
	RELCH	NM_001346231.2	MANE Select	c.440T>G	p.Met147Arg	missense	Exon 1 of 29	NP_001333160.1	A0A2R8Y566
	RELCH	NM_001346229.2		c.440T>G	p.Met147Arg	missense	Exon 1 of 30	NP_001333158.1	Q9P260-2
	RELCH	NM_001346230.2		c.440T>G	p.Met147Arg	missense	Exon 1 of 30	NP_001333159.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELCH	ENST00000644646.2	MANE Select	c.440T>G	p.Met147Arg	missense	Exon 1 of 29	ENSP00000494314.1	A0A2R8Y566
	RELCH	ENST00000398130.6	TSL:1	c.440T>G	p.Met147Arg	missense	Exon 1 of 29	ENSP00000381198.2	Q9P260-1
	RELCH	ENST00000950689.1		c.440T>G	p.Met147Arg	missense	Exon 1 of 31	ENSP00000620748.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.67
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.26
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.027
Sift	Benign	0.58	T
Sift4G	Benign	0.45	T
Polyphen		0.034	B
Vest4		0.25
MutPred		0.22		Gain of methylation at M147 (P = 0.0071)
MVP		0.24
MPC		1.1
ClinPred		0.061	T
GERP RS		3.1
Varity_R		0.31
gMVP		0.33
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs761718974; hg19: chr18-59855178;