22-35626614-C-T

Variant names:

• chr22-35626614-C-T
• rs4622835
• ENST00000447607.5:c.-8-9349G>A

Variant summary

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

The ENST00000447607.5(MB):​c.-8-9349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,160 control chromosomes in the GnomAD database, including 35,647 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 0.66 (35647 hom., cov: 33)
• Consequence: MB ENST00000447607.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

Genes affected

MB (HGNC:6915): (myoglobin) This gene encodes a member of the globin superfamily and is predominantly expressed in skeletal and cardiac muscles. The encoded protein forms a monomeric globular haemoprotein that is primarily responsible for the storage and facilitated transfer of oxygen from the cell membrane to the mitochondria. This protein also plays a role in regulating physiological levels of nitric oxide. Multiple transcript variants encoding distinct isoforms exist for this gene. [provided by RefSeq, May 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MB	ENST00000447607.5	c.-8-9349G>A		intron_variant	Intron 2 of 3	3		ENSP00000389263.1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101062 AN: 152042 Hom.: 35586 Cov.: 33

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.626

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.665 AC: 101179 AN: 152160 Hom.: 35647 Cov.: 33 AF XY: 0.670 AC XY: 49802 AN XY: 74368

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.630

Alfa AF: 0.608 Hom.: 4539

Bravo AF: 0.677

Asia WGS AF: 0.833 AC: 2898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4622835; hg19: chr22-36022661; COSMIC: COSV63094053;