18-62281158-A-C

Variant names:

• chr18-62281158-A-C
• rs1506326
• NM_001346231.2:c.3114+449A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001346231.2(RELCH):​c.3114+449A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,226 control chromosomes in the GnomAD database, including 2,787 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2787 hom., cov: 32)
• Consequence: RELCH NM_001346231.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELCH	NM_001346231.2	MANE Select	c.3114+449A>C		intron	N/A	NP_001333160.1
	RELCH	NM_001346229.2		c.3216+449A>C		intron	N/A	NP_001333158.1
	RELCH	NM_001346230.2		c.3138+449A>C		intron	N/A	NP_001333159.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RELCH	ENST00000644646.2	MANE Select	c.3114+449A>C		intron	N/A	ENSP00000494314.1
	RELCH	ENST00000398130.6	TSL:1	c.3114+449A>C		intron	N/A	ENSP00000381198.2
	RELCH	ENST00000256858.10	TSL:5	c.3216+449A>C		intron	N/A	ENSP00000256858.5

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25970 AN: 152108 Hom.: 2786 Cov.: 32

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.171 AC: 25987 AN: 152226 Hom.: 2787 Cov.: 32 AF XY: 0.168 AC XY: 12508 AN XY: 74422

African (AFR) AF: 0.0700 AC: 2909 AN: 41540

American (AMR) AF: 0.149 AC: 2272 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 865 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5186

South Asian (SAS) AF: 0.107 AC: 516 AN: 4830

European-Finnish (FIN) AF: 0.238 AC: 2520 AN: 10594

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.238 AC: 16187 AN: 68010

Other (OTH) AF: 0.193 AC: 408 AN: 2110

Alfa AF: 0.193 Hom.: 713

Bravo AF: 0.161

Asia WGS AF: 0.0700 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.75
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1506326; hg19: chr18-59948391;