2-171523426-G-C

Variant names:

• chr2-171523426-G-C
• rs960748
• NM_024843.4:c.193+688G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024843.4(CYBRD1):​c.193+688G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYBRD1 NM_024843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 24 publications found

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]

CYBRD1 Gene-Disease associations (from GenCC):

• hereditary hemochromatosis

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBRD1	NM_024843.4	MANE Select	c.193+688G>C		intron	N/A	NP_079119.3
	CYBRD1	NM_001256909.2		c.19+1135G>C		intron	N/A	NP_001243838.1
	CYBRD1	NM_001127383.2		c.193+688G>C		intron	N/A	NP_001120855.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYBRD1	ENST00000321348.9	TSL:1 MANE Select	c.193+688G>C		intron	N/A	ENSP00000319141.4
	CYBRD1	ENST00000375252.3	TSL:1	c.193+688G>C		intron	N/A	ENSP00000364401.3
	CYBRD1	ENST00000409484.5	TSL:2	c.19+1135G>C		intron	N/A	ENSP00000386739.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 68870 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 38016

African (AFR) AF: 0.00 AC: 0 AN: 342

American (AMR) AF: 0.00 AC: 0 AN: 692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1150

East Asian (EAS) AF: 0.00 AC: 0 AN: 204

South Asian (SAS) AF: 0.00 AC: 0 AN: 14830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1806

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 32752

Other (OTH) AF: 0.00 AC: 0 AN: 2808

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.5
DANN	Benign	0.67
PhyloP100		0.24
PromoterAI		0.22	Neutral

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

Other links and lift over

dbSNP: rs960748; hg19: chr2-172379936;