Variant 18-74263490-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_148923.4(CYB5A):c.130-13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00698 in 1,613,948 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 97 hom. )

Consequence

CYB5A
NM_148923.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.40

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:

CYB5A (HGNC:):

CYB5A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 18-74263490-G-T is Benign according to our data. Variant chr18-74263490-G-T is described in ClinVar as [Benign]. Clinvar id is 1600582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CYB5A	NM_148923.4 linkuse as main transcript	c.130-13C>A	intron_variant	ENST00000340533.9	NP_683725.1	P00167-1A0A384ME44
CYB5A	NM_001190807.3 linkuse as main transcript	c.130-13C>A	intron_variant		NP_001177736.1	P00167-3
CYB5A	NM_001914.4 linkuse as main transcript	c.130-13C>A	intron_variant		NP_001905.1	P00167-2
CYB5A	XM_011525835.3 linkuse as main transcript	c.130-13C>A	intron_variant		XP_011524137.1	P00167-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5A	ENST00000340533.9 linkuse as main transcript	c.130-13C>A		intron_variant		1	NM_148923.4	ENSP00000341625.4		P00167-1

Frequencies

GnomAD3 genomes

AF:

0.00582

AC:

886

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.00629

Gnomad ASJ

AF:

0.0401

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.000755

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00703

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00731

AC:

1836

AN:

251160

Hom.:

AF XY:

0.00797

AC XY:

1082

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00422

Gnomad ASJ exome

AF:

0.0416

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0135

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00659

Gnomad OTH exome

AF:

0.00995

GnomAD4 exome

AF:

0.00710

AC:

10379

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00744

AC XY:

5410

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00458

Gnomad4 ASJ exome

AF:

0.0444

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0141

Gnomad4 FIN exome

AF:

0.00135

Gnomad4 NFE exome

AF:

0.00629

Gnomad4 OTH exome

AF:

0.00980

GnomAD4 genome

AF:

0.00583

AC:

888

AN:

152270

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

399

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00628

Gnomad4 ASJ

AF:

0.0401

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.000755

Gnomad4 NFE

AF:

0.00704

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00637

Asia WGS

AF:

0.00231

AC:

AN:

3478

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 24, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

DANN

Benign

0.50

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over