rs200303151

Variant names:

• chrX-14845063-A-G
• rs200303151
• NM_001018113.3:c.1720T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-14845063-A-G
• chrX-14845063-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000650831.1(FANCB):​c.1720T>C​(p.Cys574Arg) variant causes a missense 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. 14/19 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. C574S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 24)
• Consequence: FANCB ENST00000650831.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807
• Publications: 0 publications found

Genes affected

FANCB (HGNC:3583): (FA complementation group B) This gene encodes a member of the Fanconi anemia complementation group B. This protein is assembled into a nucleoprotein complex that is involved in the repair of DNA lesions. Mutations in this gene can cause chromosome instability and VACTERL syndrome with hydrocephalus. [provided by RefSeq, Apr 2016]

FANCB Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group B

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• VACTERL association, X-linked, with or without hydrocephalus

  Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• VACTERL with hydrocephalus

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083518416).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650831.1. 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
	FANCB	NM_001018113.3	MANE Select	c.1720T>C	p.Cys574Arg	missense	Exon 8 of 10	NP_001018123.1
	FANCB	NM_001410764.1		c.1720T>C	p.Cys574Arg	missense	Exon 8 of 13	NP_001397693.1
	FANCB	NM_001324162.2		c.1720T>C	p.Cys574Arg	missense	Exon 8 of 10	NP_001311091.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCB	ENST00000650831.1	MANE Select	c.1720T>C	p.Cys574Arg	missense	Exon 8 of 10	ENSP00000498215.1
	FANCB	ENST00000324138.7	TSL:1	c.1720T>C	p.Cys574Arg	missense	Exon 7 of 9	ENSP00000326819.3
	FANCB	ENST00000452869.2	TSL:1	c.1720T>C	p.Cys574Arg	missense	Exon 8 of 11	ENSP00000397849.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00 AC: 0 AN: 183094 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.78
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.81
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.052
Sift	Benign	0.58	T
Sift4G	Benign	0.89	T
Polyphen		0.92	P
Vest4		0.21
MutPred		0.29		Gain of disorder (P = 0.0249)
MVP		0.30
MPC		0.42
ClinPred		0.66	D
GERP RS		2.8
Varity_R		0.42
Mutation Taster		=97/3	polymorphism

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: rs200303151; hg19: chrX-14863185;