Variant rs7238987 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_148923.4(CYB5A):c.288G>A(p.Pro96Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,608,572 control chromosomes in the GnomAD database, including 21,414 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1863 hom., cov: 33)

Exomes 𝑓: 0.16 ( 19551 hom. )

Consequence

CYB5A
NM_148923.4 splice_region, synonymous

Scores

Splicing: ADA: 0.2584

Clinical Significance

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

Conservation

PhyloP100: 1.65

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 18-74260915-C-T is Benign according to our data. Variant chr18-74260915-C-T is described in ClinVar as [Benign]. Clinvar id is 1600597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.65 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYB5A	NM_148923.4 linkuse as main transcript	c.288G>A	p.Pro96Pro	splice_region_variant, synonymous_variant	3/5	ENST00000340533.9	NP_683725.1	P00167-1A0A384ME44
CYB5A	NM_001914.4 linkuse as main transcript	c.288G>A	p.Pro96Pro	splice_region_variant, synonymous_variant	3/6		NP_001905.1	P00167-2
CYB5A	XM_011525835.3 linkuse as main transcript	c.288G>A	p.Pro96Pro	splice_region_variant, synonymous_variant	3/4		XP_011524137.1	P00167-2
CYB5A	NM_001190807.3 linkuse as main transcript	c.258+2434G>A		intron_variant			NP_001177736.1	P00167-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYB5A	ENST00000340533.9 linkuse as main transcript	c.288G>A	p.Pro96Pro	splice_region_variant, synonymous_variant	3/5	1	NM_148923.4	ENSP00000341625.4		P00167-1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23288

AN:

151978

Hom.:

1856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.0859

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.132

GnomAD3 exomes

AF:

0.157

AC:

39337

AN:

251228

Hom.:

3464

AF XY:

0.152

AC XY:

20690

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.241

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.0794

Gnomad SAS exome

AF:

0.139

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.160

AC:

232796

AN:

1456476

Hom.:

19551

Cov.:

AF XY:

0.158

AC XY:

114687

AN XY:

724832

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.240

Gnomad4 ASJ exome

AF:

0.0975

Gnomad4 EAS exome

AF:

0.0824

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.153

AC:

23311

AN:

152096

Hom.:

1863

Cov.:

AF XY:

0.154

AC XY:

11414

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.212

Gnomad4 ASJ

AF:

0.100

Gnomad4 EAS

AF:

0.0859

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.146

Hom.:

3626

Bravo

AF:

0.156

Asia WGS

AF:

0.120

AC:

419

AN:

3478

EpiCase

AF:

0.136

EpiControl

AF:

0.137

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.26

dbscSNV1_RF

Benign

0.49

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