rs9948708

Positions:

• chr18-62197888-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001346231.2(RELCH):​c.526+9857G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,002 control chromosomes in the GnomAD database, including 13,160 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 0.41 (13160 hom., cov: 32)
• Consequence: RELCH NM_001346231.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELCH	NM_001346231.2	c.526+9857G>A		intron_variant		ENST00000644646.2	NP_001333160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELCH	ENST00000644646.2	c.526+9857G>A		intron_variant			NM_001346231.2	ENSP00000494314	P3
RELCH	ENST00000398130.6	c.526+9857G>A		intron_variant		1		ENSP00000381198	A1
RELCH	ENST00000256858.10	c.526+9857G>A		intron_variant		5		ENSP00000256858
RELCH	ENST00000587725.5	c.526+9857G>A		intron_variant		2		ENSP00000468816

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62770 AN: 151884 Hom.: 13135 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.413 AC: 62850 AN: 152002 Hom.: 13160 Cov.: 32 AF XY: 0.413 AC XY: 30710 AN XY: 74294

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.435

Alfa AF: 0.418 Hom.: 18439

Bravo AF: 0.401

Asia WGS AF: 0.410 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.079
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs9948708; hg19: chr18-59865121;