2-171523426-G-A

Position:

• chr2-171523426-G-A

Variant summary

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

The NM_024843.4(CYBRD1):​c.193+688G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 220,412 control chromosomes in the GnomAD database, including 39,638 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 0.62 (30220 hom., cov: 32)
  • Exomes 𝑓: 0.52 (9418 hom.)
• Consequence: CYBRD1 NM_024843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

Genes affected

CYBRD1 (HGNC:20797): (cytochrome b reductase 1) This gene is a member of the cytochrome b(561) family that encodes an iron-regulated protein. It highly expressed in the duodenal brush border membrane. It has ferric reductase activity and is believed to play a physiological role in dietary iron absorption. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYBRD1	NM_024843.4	c.193+688G>A		intron_variant		ENST00000321348.9
CYBRD1	NM_001127383.2	c.193+688G>A		intron_variant
CYBRD1	NM_001256909.2	c.19+1135G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYBRD1	ENST00000321348.9	c.193+688G>A		intron_variant		1	NM_024843.4	P1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94747 AN: 151936 Hom.: 30188 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.591

GnomAD4 exome AF: 0.516 AC: 35252 AN: 68358 Hom.: 9418 AF XY: 0.522 AC XY: 19686 AN XY: 37714

Gnomad4 AFR exome AF: 0.645

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.876

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.515

GnomAD4 genome AF: 0.624 AC: 94836 AN: 152054 Hom.: 30220 Cov.: 32 AF XY: 0.627 AC XY: 46571 AN XY: 74314

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.587

Alfa AF: 0.560 Hom.: 47459

Bravo AF: 0.636

Asia WGS AF: 0.702 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.7
DANN	Benign	0.84
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

Other links and lift over

dbSNP: rs960748; hg19: chr2-172379936;