2-171523426-G-T

Variant names:

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

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>T 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)
• 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=-0.77).

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>T		intron	N/A	NP_079119.3
	CYBRD1	NM_001256909.2		c.19+1135G>T		intron	N/A	NP_001243838.1
	CYBRD1	NM_001127383.2		c.193+688G>T		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>T		intron	N/A	ENSP00000319141.4
	CYBRD1	ENST00000375252.3	TSL:1	c.193+688G>T		intron	N/A	ENSP00000364401.3
	CYBRD1	ENST00000409484.5	TSL:2	c.19+1135G>T		intron	N/A	ENSP00000386739.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 101749

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.3
DANN	Benign	0.74
PhyloP100		0.24
PromoterAI		0.17	Neutral
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

Other links and lift over

dbSNP: rs960748; hg19: chr2-172379936;