Genetic Variant RELCH:p.Ser76Leu (chr18-62187732-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001346235.2(RELCH):c.-2147C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000686 in 1,456,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

RELCH
NM_001346235.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

Publications

0 publications found

Variant links:

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]

RELCH links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1809757).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346235.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RELCH	NM_001346231.2	MANE Select	c.227C>T	p.Ser76Leu	missense	Exon 1 of 29	NP_001333160.1	A0A2R8Y566
RELCH	NM_001346235.2		c.-2147C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 31	NP_001333164.1
RELCH	NM_001346229.2		c.227C>T	p.Ser76Leu	missense	Exon 1 of 30	NP_001333158.1	Q9P260-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RELCH	ENST00000644646.2	MANE Select	c.227C>T	p.Ser76Leu	missense	Exon 1 of 29	ENSP00000494314.1	A0A2R8Y566
RELCH	ENST00000398130.6	TSL:1	c.227C>T	p.Ser76Leu	missense	Exon 1 of 29	ENSP00000381198.2	Q9P260-1
RELCH	ENST00000950689.1		c.227C>T	p.Ser76Leu	missense	Exon 1 of 31	ENSP00000620748.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

241386

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1456812

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

724022

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33376

American (AMR)

AF:

0.00

AC:

AN:

44352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25954

East Asian (EAS)

AF:

0.00

AC:

AN:

39580

South Asian (SAS)

AF:

0.0000582

AC:

AN:

85966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1108690

Other (OTH)

AF:

0.0000167

AC:

AN:

60038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.80

M_CAP

Benign

0.0089

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

PhyloP100

4.6

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.0

REVEL

Benign

0.026

Sift

Benign

0.037

Sift4G

Benign

0.32

Polyphen

0.023

Vest4

0.19

MutPred

0.32

Loss of glycosylation at S76 (P = 0.0023)

MVP

0.082

MPC

0.65

ClinPred

0.67

GERP RS

4.5

PromoterAI

0.00020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.31

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over