chr2-171554763-G-A

Position:

• chr2-171554763-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024843.4(CYBRD1):​c.797G>A​(p.Ser266Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 1,613,702 control chromosomes in the GnomAD database, including 361,957 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.71 (39429 hom., cov: 32)
  • Exomes 𝑓: 0.66 (322528 hom.)
• Consequence: CYBRD1 NM_024843.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.5515926E-7).
• BP6: Variant 2-171554763-G-A is Benign according to our data. Variant chr2-171554763-G-A is described in ClinVar as [Benign]. Clinvar id is 1237711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYBRD1	NM_024843.4	c.797G>A	p.Ser266Asn	missense_variant	4/4	ENST00000321348.9	NP_079119.3
CYBRD1	NM_001256909.2	c.623G>A	p.Ser208Asn	missense_variant	4/4		NP_001243838.1
CYBRD1	NM_001127383.2	c.*114G>A		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>A	p.Ser266Asn	missense_variant	4/4	1	NM_024843.4	ENSP00000319141.4
CYBRD1	ENST00000375252.3	c.*114G>A		3_prime_UTR_variant	3/3	1		ENSP00000364401.3
CYBRD1	ENST00000409484.5	c.623G>A	p.Ser208Asn	missense_variant	4/4	2		ENSP00000386739.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107792 AN: 151952 Hom.: 39385 Cov.: 32

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.656

GnomAD3 exomes AF: 0.641 AC: 160756 AN: 250712 Hom.: 53120 AF XY: 0.641 AC XY: 86828 AN XY: 135494

Gnomad AFR exome AF: 0.888

Gnomad AMR exome AF: 0.579

Gnomad ASJ exome AF: 0.589

Gnomad EAS exome AF: 0.375

Gnomad SAS exome AF: 0.660

Gnomad FIN exome AF: 0.626

Gnomad NFE exome AF: 0.671

Gnomad OTH exome AF: 0.632

GnomAD4 exome AF: 0.661 AC: 965561 AN: 1461628 Hom.: 322528 Cov.: 61 AF XY: 0.659 AC XY: 479435 AN XY: 727126

Gnomad4 AFR exome AF: 0.889

Gnomad4 AMR exome AF: 0.583

Gnomad4 ASJ exome AF: 0.589

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.648

GnomAD4 genome AF: 0.710 AC: 107897 AN: 152074 Hom.: 39429 Cov.: 32 AF XY: 0.706 AC XY: 52437 AN XY: 74324

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.654

Alfa AF: 0.664 Hom.: 83925

Bravo AF: 0.711

TwinsUK AF: 0.684 AC: 2536

ALSPAC AF: 0.672 AC: 2589

ESP6500AA AF: 0.879 AC: 3875

ESP6500EA AF: 0.659 AC: 5670

ExAC AF: 0.651 AC: 79072

Asia WGS AF: 0.595 AC: 2070 AN: 3478

EpiCase AF: 0.657

EpiControl AF: 0.659

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.13
DANN	Benign	0.42
DEOGEN2	Benign	0.085	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.14	T;T
MetaRNN	Benign	5.6e-7	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.28	.;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.060	N;N
REVEL	Benign	0.12
Sift	Benign	0.93	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.0	.;B
Vest4		0.045
MPC		0.37
ClinPred		0.0015	T
GERP RS		-3.3
Varity_R		0.026
gMVP		0.21

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; COSMIC: COSV58426537; COSMIC: COSV58426537;