rs1051236

chr18-74291840-G-Achr18-74291840-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_148923.4(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 NM_148923.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.826

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]

ACMG classification

Verdict is Benign. Variant got -12 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_single_submitter, 1 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	UniProt
CYB5A	NM_148923.4	c.36C>T	p.Tyr12=	synonymous_variant	1/5	ENST00000340533.9
CYB5A	NM_001190807.3	c.36C>T	p.Tyr12=	synonymous_variant	1/4
CYB5A	NM_001914.4	c.36C>T	p.Tyr12=	synonymous_variant	1/6
CYB5A	XM_011525835.3	c.36C>T	p.Tyr12=	synonymous_variant	1/4

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18055 AN: 152026 Hom.: 1387 Cov.: 32

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

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.: 33 AF XY: 0.157 AC XY: 114457 AN XY: 727056

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.: 32 AF XY: 0.120 AC XY: 8924 AN XY: 74348

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	13
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

Other links and lift over

dbSNP: rs1051236; hg19: chr18-71959075; COSMIC: COSV55021885; COSMIC: COSV55021885;