Variant 18-62187574-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001346231.2(RELCH):c.69T>A(p.Asp23Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,523,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

RELCH
NM_001346231.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.515

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:

RELCH (HGNC:):

RELCH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024160802).

BS2

High AC in GnomAd4 at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RELCH	NM_001346231.2 linkuse as main transcript	c.69T>A	p.Asp23Glu	missense_variant	1/29	ENST00000644646.2	NP_001333160.1	A0A2R8Y566

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RELCH	ENST00000644646.2 linkuse as main transcript	c.69T>A	p.Asp23Glu	missense_variant	1/29		NM_001346231.2	ENSP00000494314.1	A0A2R8Y566
RELCH	ENST00000398130.6 linkuse as main transcript	c.69T>A	p.Asp23Glu	missense_variant	1/29	1		ENSP00000381198.2	Q9P260-1
RELCH	ENST00000256858.10 linkuse as main transcript	c.69T>A	p.Asp23Glu	missense_variant	1/30	5		ENSP00000256858.5	Q9P260-2
RELCH	ENST00000587725.5 linkuse as main transcript	n.69T>A		non_coding_transcript_exon_variant	1/22	2		ENSP00000468816.1	A0A075B785

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000256

AC:

AN:

179992

Hom.:

AF XY:

0.000241

AC XY:

AN XY:

95496

show subpopulations

Gnomad AFR exome

AF:

0.0000681

Gnomad AMR exome

AF:

0.000420

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.000739

GnomAD4 exome

AF:

0.000257

AC:

352

AN:

1371010

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

152

AN XY:

672536

show subpopulations

Gnomad4 AFR exome

AF:

0.0000989

Gnomad4 AMR exome

AF:

0.000370

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000200

Gnomad4 NFE exome

AF:

0.000303

Gnomad4 OTH exome

AF:

0.000231

GnomAD4 genome

AF:

0.000394

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000879

Hom.:

Bravo

AF:

0.000400

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000709

AC:

ExAC

AF:

0.000218

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.69T>A (p.D23E) alteration is located in exon 1 (coding exon 1) of the KIAA1468 gene. This alteration results from a T to A substitution at nucleotide position 69, causing the aspartic acid (D) at amino acid position 23 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.024

.;.;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.51

.;N;N

REVEL

Benign

0.096

Sift

Benign

0.40

.;T;T

Sift4G

Benign

0.89

.;T;T

Polyphen

0.0010, 0.0

.;B;B

Vest4

0.17, 0.13

MutPred

0.046

Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);

MVP

0.082

MPC

0.67

ClinPred

0.034

GERP RS

-0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.042

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over