Variant 16-1834371-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001163560.3(MEIOB):c.1306-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 1,484,288 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0048 ( 26 hom. )

Consequence

MEIOB
NM_001163560.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006780

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.801

Variant links:

Genes affected

MEIOB (HGNC:28569): (meiosis specific with OB-fold) Predicted to enable chromatin binding activity; single-stranded DNA 3'-5' exodeoxyribonuclease activity; and single-stranded DNA binding activity. Predicted to be involved in double-strand break repair via homologous recombination; fertilization; and meiotic nuclear division. Predicted to be located in cytoplasm. Implicated in spermatogenic failure 22. [provided by Alliance of Genome Resources, Apr 2022]

MEIOB links:

FAHD1 (HGNC:14169): (fumarylacetoacetate hydrolase domain containing 1) Enables acetylpyruvate hydrolase activity; fumarylpyruvate hydrolase activity; and oxaloacetate decarboxylase activity. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAHD1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 16-1834371-G-A is Benign according to our data. Variant chr16-1834371-G-A is described in ClinVar as [Benign]. Clinvar id is 715773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIOB	NM_001163560.3 linkuse as main transcript	c.1306-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000325962.9	NP_001157032.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIOB	ENST00000325962.9 linkuse as main transcript	c.1306-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001163560.3	ENSP00000314484	P1	Q8N635-2
	ENST00000470044.5 linkuse as main transcript	c.685-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000457416	P1

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

539

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00102

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00519

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00366

AC:

854

AN:

233352

Hom.:

AF XY:

0.00368

AC XY:

464

AN XY:

126052

show subpopulations

Gnomad AFR exome

AF:

0.000877

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00766

Gnomad EAS exome

AF:

0.0000569

Gnomad SAS exome

AF:

0.00449

Gnomad FIN exome

AF:

0.00178

Gnomad NFE exome

AF:

0.00492

Gnomad OTH exome

AF:

0.00667

GnomAD4 exome

AF:

0.00483

AC:

6434

AN:

1332246

Hom.:

Cov.:

AF XY:

0.00488

AC XY:

3264

AN XY:

668354

show subpopulations

Gnomad4 AFR exome

AF:

0.000528

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.00809

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00542

Gnomad4 FIN exome

AF:

0.00231

Gnomad4 NFE exome

AF:

0.00524

Gnomad4 OTH exome

AF:

0.00542

GnomAD4 genome

AF:

0.00355

AC:

539

AN:

152042

Hom.:

Cov.:

AF XY:

0.00330

AC XY:

245

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00102

Gnomad4 AMR

AF:

0.00465

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00519

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00401

Hom.:

Bravo

AF:

0.00348

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00465

EpiControl

AF:

0.00512

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	Jul 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.9

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000068

dbscSNV1_RF

Benign

0.0

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

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