Variant chr11-122115672-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001786.3(BLID):c.251A>C(p.His84Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

BLID
NM_001001786.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.467

Variant links:

Genes affected

BLID (HGNC:33495): (BH3-like motif containing, cell death inducer) This gene encodes a BH3-like motif containing protein involved in cell death. The encoded protein may induce apoptosis in a caspase-dependent manner. The protein is localized in both the cytoplasm and the mitochondrion. [provided by RefSeq, Aug 2011]

BLID links:

MIR100HG (HGNC:39522): (mir-100-let-7a-2-mir-125b-1 cluster host gene) This gene produces long non-coding RNAs that act as regulators of cell proliferation. Alternative promoter usage and splicing results in multiple transcript variants. Some transcript variants may promote growth, while others may act to negatively regulate cell division. [provided by RefSeq, May 2016]

MIR100HG links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12048626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLID	NM_001001786.3 linkuse as main transcript	c.251A>C	p.His84Pro	missense_variant	1/1	ENST00000560104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLID	ENST00000560104.2 linkuse as main transcript	c.251A>C	p.His84Pro	missense_variant	1/1		NM_001001786.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251378

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000145

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000499

AC:

AN:

1461696

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Feb 14, 2023

The c.251A>C (p.H84P) alteration is located in exon 1 (coding exon 1) of the BLID gene. This alteration results from a A to C substitution at nucleotide position 251, causing the histidine (H) at amino acid position 84 to be replaced by a proline (P). 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

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.093

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.22

M_CAP

Benign

0.0089

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-6.7

Polyphen

0.21

Vest4

0.33

MutPred

0.35

Gain of disorder (P = 0.0353);

MVP

0.86

MPC

0.079

ClinPred

0.063

GERP RS

0.16

Varity_R

0.68

gMVP

0.038

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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