rs17288294

Positions:

• chr2-171546765-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.402+4972C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,034 control chromosomes in the GnomAD database, including 1,912 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 0.15 (1912 hom., cov: 31)
• Consequence: CYBRD1 NM_024843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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 (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBRD1	NM_024843.4	c.402+4972C>T		intron_variant		ENST00000321348.9	NP_079119.3
CYBRD1	NM_001127383.2	c.194-6581C>T		intron_variant			NP_001120855.1
CYBRD1	NM_001256909.2	c.228+4972C>T		intron_variant			NP_001243838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBRD1	ENST00000321348.9	c.402+4972C>T		intron_variant		1	NM_024843.4	ENSP00000319141	P1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22957 AN: 151916 Hom.: 1912 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0743

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.151 AC: 22959 AN: 152034 Hom.: 1912 Cov.: 31 AF XY: 0.156 AC XY: 11567 AN XY: 74320

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0749

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.142

Alfa AF: 0.163 Hom.: 274

Bravo AF: 0.138

Asia WGS AF: 0.111 AC: 386 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	5.1
DANN	Benign	0.80

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: rs17288294; hg19: chr2-172403275;