Genetic Variant FANCB:c.1327-3dupT (chrX-14850676-T-TA) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_001018113.3(FANCB):c.1327-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000825 in 1,045,956 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., 3 hem., cov: 21)

Exomes 𝑓: 0.00091 ( 0 hom. 12 hem. )

Consequence

FANCB
NM_001018113.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.476

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant X-14850676-T-TA is Benign according to our data. Variant chrX-14850676-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 1169946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCB	NM_001018113.3 link	c.1327-3dupT		splice_region_variant, intron_variant	Intron 6 of 9	ENST00000650831.1	NP_001018123.1	Q8NB91A0A024RBW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCB	ENST00000650831.1 link	c.1327-3_1327-2insT		splice_region_variant, intron_variant	Intron 6 of 9		NM_001018113.3	ENSP00000498215.1		Q8NB91

Frequencies

GnomAD3 genomes

AF:

0.0000853

AC:

AN:

105514

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

29624

show subpopulations

Gnomad AFR

AF:

0.0000347

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000594

Gnomad SAS

AF:

0.00162

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000195

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000908

AC:

854

AN:

940414

Hom.:

Cov.:

AF XY:

0.0000452

AC XY:

AN XY:

265734

show subpopulations

Gnomad4 AFR exome

AF:

0.000526

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.000527

Gnomad4 EAS exome

AF:

0.000553

Gnomad4 SAS exome

AF:

0.00162

Gnomad4 FIN exome

AF:

0.000107

Gnomad4 NFE exome

AF:

0.000964

Gnomad4 OTH exome

AF:

0.000626

GnomAD4 genome

AF:

0.0000853

AC:

AN:

105542

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

29666

show subpopulations

Gnomad4 AFR

AF:

0.0000346

Gnomad4 AMR

AF:

0.000103

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000596

Gnomad4 SAS

AF:

0.00163

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000195

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia

Benign:2

Jun 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 17, 2021

Sema4, Sema4

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

not specified

Benign:1

Aug 24, 2021

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

X-14850676-TAAA-TAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over