16-1850704-C-T

Variant names:

• chr16-1850704-C-T
• rs1742417
• NM_001163560.3:c.778+2335G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001163560.3(MEIOB):​c.778+2335G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 151,518 control chromosomes in the GnomAD database, including 35,239 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.68 (35239 hom., cov: 30)
• Consequence: MEIOB NM_001163560.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure 22

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIOB	NM_001163560.3	c.778+2335G>A		intron_variant	Intron 9 of 13	ENST00000325962.9	NP_001157032.1
MEIOB	NM_152764.3	c.778+2335G>A		intron_variant	Intron 9 of 12		NP_689977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIOB	ENST00000325962.9	c.778+2335G>A		intron_variant	Intron 9 of 13	5	NM_001163560.3	ENSP00000314484.3
MEIOB	ENST00000397344.7	c.778+2335G>A		intron_variant	Intron 9 of 12	5		ENSP00000380504.3
MEIOB	ENST00000470044.5	c.157+2335G>A		intron_variant	Intron 8 of 12	2		ENSP00000457416.1
MEIOB	ENST00000496541.6	c.157+2335G>A		intron_variant	Intron 7 of 7	5		ENSP00000456880.1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103026 AN: 151402 Hom.: 35201 Cov.: 30

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.700

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.681 AC: 103126 AN: 151518 Hom.: 35239 Cov.: 30 AF XY: 0.673 AC XY: 49837 AN XY: 74052

African (AFR) AF: 0.674 AC: 27838 AN: 41324

American (AMR) AF: 0.686 AC: 10454 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2534 AN: 3460

East Asian (EAS) AF: 0.563 AC: 2900 AN: 5148

South Asian (SAS) AF: 0.644 AC: 3098 AN: 4812

European-Finnish (FIN) AF: 0.591 AC: 6167 AN: 10438

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47779 AN: 67802

Other (OTH) AF: 0.704 AC: 1482 AN: 2104

Alfa AF: 0.577 Hom.: 1578

Bravo AF: 0.693

Asia WGS AF: 0.634 AC: 2202 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.87
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs1742417; hg19: chr16-1900705;