Variant 6-42828721-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001393499.1(BICRAL):c.388A>G(p.Ile130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I130M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BICRAL
NM_001393499.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

BICRAL (HGNC:21111): (BICRA like chromatin remodeling complex associated protein) Predicted to be involved in positive regulation of transcription, DNA-templated. Part of SWI/SNF complex. [provided by Alliance of Genome Resources, Apr 2022]

BICRAL links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BICRAL	NM_001393499.1 linkuse as main transcript	c.388A>G	p.Ile130Val	missense_variant	6/13	ENST00000314073.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BICRAL	ENST00000314073.10 linkuse as main transcript	c.388A>G	p.Ile130Val	missense_variant	6/13	1	NM_001393499.1	P1
BICRAL	ENST00000394168.1 linkuse as main transcript	c.388A>G	p.Ile130Val	missense_variant	5/12	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 30, 2024

The c.388A>G (p.I130V) alteration is located in exon 5 (coding exon 4) of the GLTSCR1L gene. This alteration results from a A to G substitution at nucleotide position 388, causing the isoleucine (I) at amino acid position 130 to be replaced by a valine (V). 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

0.064

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.015

T;T;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.061

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.73

T;.;.

M_CAP

Benign

0.0028

MetaRNN

Benign

0.050

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.60

N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.11

.;N;N

REVEL

Benign

0.072

Sift

Benign

0.45

.;T;T

Sift4G

Benign

0.82

T;T;T

Polyphen

0.0090

B;B;B

Vest4

0.061

MutPred

0.12

Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.043

MPC

0.18

ClinPred

0.12

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.026

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.33

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over