Variant 14-44504920-TCTCCTCAGCTGGTAGAGACTGAACTTCAGCAGGGGC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2

The NM_032135.4(FSCB):c.2032_2067delGCCCCTGCTGAAGTTCAGTCTCTACCAGCTGAGGAG(p.Ala678_Glu689del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 150,608 control chromosomes in the GnomAD database, including 46 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 46 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 28 hom. )

Failed GnomAD Quality Control

Consequence

FSCB
NM_032135.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

FSCB (HGNC:20494): (fibrous sheath CABYR binding protein) Predicted to enable calcium ion binding activity. Predicted to be involved in negative regulation of protein sumoylation. Predicted to be active in sperm fibrous sheath and sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

FSCB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_032135.4.

BP6

Variant 14-44504920-TCTCCTCAGCTGGTAGAGACTGAACTTCAGCAGGGGC-T is Benign according to our data. Variant chr14-44504920-TCTCCTCAGCTGGTAGAGACTGAACTTCAGCAGGGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 776832.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0061 (918/150608) while in subpopulation AFR AF= 0.0215 (868/40394). AF 95% confidence interval is 0.0203. There are 46 homozygotes in gnomad4. There are 436 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FSCB	NM_032135.4 linkuse as main transcript	c.2032_2067delGCCCCTGCTGAAGTTCAGTCTCTACCAGCTGAGGAG	p.Ala678_Glu689del	conservative_inframe_deletion	1/1	ENST00000340446.5	NP_115511.3	Q5H9T9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FSCB	ENST00000340446.5 linkuse as main transcript	c.2032_2067delGCCCCTGCTGAAGTTCAGTCTCTACCAGCTGAGGAG	p.Ala678_Glu689del	conservative_inframe_deletion	1/1	6	NM_032135.4	ENSP00000344579.4		Q5H9T9

Frequencies

GnomAD3 genomes

AF:

0.00609

AC:

916

AN:

150492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00204

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.0000884

Gnomad OTH

AF:

0.00483

GnomAD3 exomes

AF:

0.000407

AC:

102

AN:

250524

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135628

show subpopulations

Gnomad AFR exome

AF:

0.00548

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000323

AC:

472

AN:

1461106

Hom.:

AF XY:

0.000272

AC XY:

198

AN XY:

726856

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.000730

GnomAD4 genome

AF:

0.00610

AC:

918

AN:

150608

Hom.:

Cov.:

AF XY:

0.00592

AC XY:

436

AN XY:

73638

show subpopulations

Gnomad4 AFR

AF:

0.0215

Gnomad4 AMR

AF:

0.00204

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000884

Gnomad4 OTH

AF:

0.00478

Alfa

AF:

0.000203

Hom.:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 04, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

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