2-171554763-G-C

Position:

• chr2-171554763-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024843.4(CYBRD1):​c.797G>C​(p.Ser266Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S266N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CYBRD1 NM_024843.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104913056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBRD1	NM_024843.4	c.797G>C	p.Ser266Thr	missense_variant	4/4	ENST00000321348.9	NP_079119.3
CYBRD1	NM_001256909.2	c.623G>C	p.Ser208Thr	missense_variant	4/4		NP_001243838.1
CYBRD1	NM_001127383.2	c.*114G>C		3_prime_UTR_variant	3/3		NP_001120855.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYBRD1	ENST00000321348.9	c.797G>C	p.Ser266Thr	missense_variant	4/4	1	NM_024843.4	ENSP00000319141.4
CYBRD1	ENST00000375252.3	c.*114G>C		3_prime_UTR_variant	3/3	1		ENSP00000364401.3
CYBRD1	ENST00000409484.5	c.623G>C	p.Ser208Thr	missense_variant	4/4	2		ENSP00000386739.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461706 Hom.: 0 Cov.: 61 AF XY: 0.00000275 AC XY: 2 AN XY: 727160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.11
DANN	Benign	0.85
DEOGEN2	Benign	0.15	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.14	T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.94	.;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.73	N;N
REVEL	Benign	0.083
Sift	Benign	0.26	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0010	.;B
Vest4		0.067
MutPred		0.096		.;Loss of phosphorylation at S266 (P = 0.0621);
MVP		0.26
MPC		0.36
ClinPred		0.084	T
GERP RS		-3.3
Varity_R		0.037
gMVP		0.25

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: rs10455; hg19: chr2-172411273;