rs2542941

Positions:

• chr2-171553211-C-T

Variant summary

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

The NM_024843.4(CYBRD1):​c.403-135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 983,600 control chromosomes in the GnomAD database, including 218,768 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 0.70 (38040 hom., cov: 33)
  • Exomes 𝑓: 0.65 (180728 hom.)
• Consequence: CYBRD1 NM_024843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYBRD1	NM_024843.4	c.403-135C>T		intron_variant		ENST00000321348.9
CYBRD1	NM_001127383.2	c.194-135C>T		intron_variant
CYBRD1	NM_001256909.2	c.229-135C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYBRD1	ENST00000321348.9	c.403-135C>T		intron_variant		1	NM_024843.4	P1
CYBRD1	ENST00000375252.3	c.194-135C>T		intron_variant		1
CYBRD1	ENST00000409484.5	c.229-135C>T		intron_variant		2
CYBRD1	ENST00000445146.1	c.286-135C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106228 AN: 152014 Hom.: 38005 Cov.: 33

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.645

GnomAD4 exome AF: 0.655 AC: 544604 AN: 831468 Hom.: 180728 AF XY: 0.654 AC XY: 279536 AN XY: 427284

Gnomad4 AFR exome AF: 0.846

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.591

Gnomad4 EAS exome AF: 0.371

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.634

Gnomad4 NFE exome AF: 0.671

Gnomad4 OTH exome AF: 0.646

GnomAD4 genome AF: 0.699 AC: 106321 AN: 152132 Hom.: 38040 Cov.: 33 AF XY: 0.695 AC XY: 51682 AN XY: 74364

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.644

Alfa AF: 0.664 Hom.: 44431

Bravo AF: 0.699

Asia WGS AF: 0.595 AC: 2070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.29

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: rs2542941; hg19: chr2-172409721;