Variant chr18-74291840-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000340533.9(CYB5A):c.36C>T(p.Tyr12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,613,590 control chromosomes in the GnomAD database, including 21,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1391 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19699 hom. )

Consequence

CYB5A
ENST00000340533.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.826

Variant links:

Genes affected

CYB5A (HGNC:2570): (cytochrome b5 type A) The protein encoded by this gene is a membrane-bound cytochrome that reduces ferric hemoglobin (methemoglobin) to ferrous hemoglobin, which is required for stearyl-CoA-desaturase activity. Defects in this gene are a cause of type IV hereditary methemoglobinemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

CYB5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 18-74291840-G-A is Benign according to our data. Variant chr18-74291840-G-A is described in ClinVar as [Benign]. Clinvar id is 1599637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CYB5A	NM_148923.4 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/5	ENST00000340533.9	NP_683725.1
CYB5A	NM_001190807.3 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/4		NP_001177736.1
CYB5A	NM_001914.4 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/6		NP_001905.1
CYB5A	XM_011525835.3 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/4		XP_011524137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5A	ENST00000340533.9 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/5	1	NM_148923.4	ENSP00000341625	P1	P00167-1
CYB5A	ENST00000494131.6 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/6	1		ENSP00000436461		P00167-2
CYB5A	ENST00000397914.4 linkuse as main transcript	c.36C>T	p.Tyr12=	synonymous_variant	1/4	3		ENSP00000381011		P00167-3
CYB5A	ENST00000583418.1 linkuse as main transcript	n.118C>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18055

AN:

152026

Hom.:

1387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0318

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.0920

Gnomad EAS

AF:

0.0741

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.148

AC:

37075

AN:

251354

Hom.:

3307

AF XY:

0.146

AC XY:

19783

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0294

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.0939

Gnomad EAS exome

AF:

0.0689

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.159

AC:

232308

AN:

1461446

Hom.:

19699

Cov.:

AF XY:

0.157

AC XY:

114457

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.0230

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.0905

Gnomad4 EAS exome

AF:

0.0751

Gnomad4 SAS exome

AF:

0.142

Gnomad4 FIN exome

AF:

0.175

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.139

GnomAD4 genome

AF:

0.119

AC:

18072

AN:

152144

Hom.:

1391

Cov.:

AF XY:

0.120

AC XY:

8924

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0317

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.0920

Gnomad4 EAS

AF:

0.0742

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.168

Gnomad4 NFE

AF:

0.153

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.132

Hom.:

744

Bravo

AF:

0.115

Asia WGS

AF:

0.107

AC:

373

AN:

3478

EpiCase

AF:

0.137

EpiControl

AF:

0.138

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over