2-171522379-C-G

Variant names:

• chr2-171522379-C-G
• rs2356782
• NM_001256909.2:c.19+88C>G

Variant summary

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

The NM_001256909.2(CYBRD1):​c.19+88C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,491,972 control chromosomes in the GnomAD database, including 247,693 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 0.63 (31392 hom., cov: 32)
  • Exomes 𝑓: 0.56 (216301 hom.)
• Consequence: CYBRD1 NM_001256909.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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=-0.77).
• 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 rank	MANE	Protein	UniProt
CYBRD1	NM_001256909.2	c.19+88C>G		intron_variant	Intron 1 of 3		NP_001243838.1
CYBRD1	NM_024843.4	c.-167C>G		upstream_gene_variant		ENST00000321348.9	NP_079119.3
CYBRD1	NM_001127383.2	c.-167C>G		upstream_gene_variant			NP_001120855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYBRD1	ENST00000321348.9	c.-167C>G		upstream_gene_variant		1	NM_024843.4	ENSP00000319141.4

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96324 AN: 151808 Hom.: 31359 Cov.: 32

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.564 AC: 755754 AN: 1340046 Hom.: 216301 Cov.: 60 AF XY: 0.565 AC XY: 370307 AN XY: 655288

Gnomad4 AFR exome AF: 0.785

Gnomad4 AMR exome AF: 0.627

Gnomad4 ASJ exome AF: 0.567

Gnomad4 EAS exome AF: 0.843

Gnomad4 SAS exome AF: 0.643

Gnomad4 FIN exome AF: 0.569

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.635 AC: 96414 AN: 151926 Hom.: 31392 Cov.: 32 AF XY: 0.637 AC XY: 47348 AN XY: 74272

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.597

Alfa AF: 0.501 Hom.: 1517

Bravo AF: 0.648

Asia WGS AF: 0.708 AC: 2463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.0
DANN	Benign	0.74

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: rs2356782; hg19: chr2-172378889;