Variant 1-93901541-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002061.4(GCLM):c.277+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 975,892 control chromosomes in the GnomAD database, including 69,074 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 0.44 ( 16906 hom., cov: 32)

Exomes 𝑓: 0.35 ( 52168 hom. )

Consequence

GCLM
NM_002061.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0810

Variant links:

Genes affected

GCLM (HGNC:4312): (glutamate-cysteine ligase modifier subunit) Glutamate-cysteine ligase, also known as gamma-glutamylcysteine synthetase, is the first rate limiting enzyme of glutathione synthesis. The enzyme consists of two subunits, a heavy catalytic subunit and a light regulatory subunit. Gamma glutamylcysteine synthetase deficiency has been implicated in some forms of hemolytic anemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

GCLM links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
GCLM	NM_002061.4 linkuse as main transcript	c.277+44C>T	intron_variant	ENST00000370238.8
GCLM	NM_001308253.2 linkuse as main transcript	c.211+44C>T	intron_variant
GCLM	XM_011541261.3 linkuse as main transcript	c.13+44C>T	intron_variant
GCLM	XM_047418031.1 linkuse as main transcript	c.277+44C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
GCLM	ENST00000370238.8 linkuse as main transcript	c.277+44C>T	intron_variant	1	NM_002061.4	P1	P48507-1
GCLM	ENST00000615724.1 linkuse as main transcript	c.211+44C>T	intron_variant	1			P48507-2
GCLM	ENST00000467772.1 linkuse as main transcript	n.277+44C>T	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67509

AN:

151840

Hom.:

16871

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.312

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.223

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.362

AC:

82965

AN:

229424

Hom.:

16583

AF XY:

0.348

AC XY:

43332

AN XY:

124528

show subpopulations

Gnomad AFR exome

AF:

0.690

Gnomad AMR exome

AF:

0.477

Gnomad ASJ exome

AF:

0.312

Gnomad EAS exome

AF:

0.207

Gnomad SAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.349

Gnomad NFE exome

AF:

0.349

Gnomad OTH exome

AF:

0.343

GnomAD4 exome

AF:

0.346

AC:

284685

AN:

823934

Hom.:

52168

Cov.:

AF XY:

0.339

AC XY:

147705

AN XY:

435296

show subpopulations

Gnomad4 AFR exome

AF:

0.691

Gnomad4 AMR exome

AF:

0.472

Gnomad4 ASJ exome

AF:

0.318

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.350

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

AF:

0.445

AC:

67600

AN:

151958

Hom.:

16906

Cov.:

AF XY:

0.442

AC XY:

32844

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.681

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.223

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.371

Hom.:

10962

Bravo

AF:

0.467

Asia WGS

AF:

0.247

AC:

858

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.75

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over