rs77442034

Variant names:

• chr18-74292089-G-A
• rs77442034
• NM_148923.4:c.-214C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-74292089-G-A
• chr18-74292089-G-C
• chr18-74292089-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_148923.4(CYB5A):​c.-214C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 657,600 control chromosomes in the GnomAD database, including 7,224 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 0.12 (1392 hom., cov: 33)
  • Exomes 𝑓: 0.14 (5832 hom.)
• Consequence: CYB5A NM_148923.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.8).
• 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 rank	MANE	Protein	UniProt
CYB5A	NM_148923.4	c.-214C>T		upstream_gene_variant		ENST00000340533.9	NP_683725.1
CYB5A	NM_001190807.3	c.-214C>T		upstream_gene_variant			NP_001177736.1
CYB5A	NM_001914.4	c.-214C>T		upstream_gene_variant			NP_001905.1
CYB5A	XM_011525835.3	c.-214C>T		upstream_gene_variant			XP_011524137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYB5A	ENST00000340533.9	c.-214C>T		upstream_gene_variant		1	NM_148923.4	ENSP00000341625.4
CYB5A	ENST00000494131.6	c.-214C>T		upstream_gene_variant		1		ENSP00000436461.2
CYB5A	ENST00000397914.4	c.-214C>T		upstream_gene_variant		3		ENSP00000381011.4
CYB5A	ENST00000583418.1	n.-132C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18072 AN: 152140 Hom.: 1388 Cov.: 33

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.144 AC: 72685 AN: 505342 Hom.: 5832 AF XY: 0.143 AC XY: 38423 AN XY: 267758

Gnomad4 AFR exome AF: 0.0283

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.0913

Gnomad4 EAS exome AF: 0.0744

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.119 AC: 18089 AN: 152258 Hom.: 1392 Cov.: 33 AF XY: 0.120 AC XY: 8938 AN XY: 74440

Gnomad4 AFR AF: 0.0317

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.0922

Gnomad4 EAS AF: 0.0739

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0577 Hom.: 66

Bravo AF: 0.115

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.0
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77442034; hg19: chr18-71959324;