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rs1800469

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000539627.5(TMEM91):c.-30+3189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 590,170 control chromosomes in the GnomAD database, including 133,128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36451 hom., cov: 31)
Exomes 𝑓: 0.66 ( 96677 hom. )

Consequence

TMEM91
ENST00000539627.5 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -1.81
Variant links:
Genes affected
TMEM91 (HGNC:32393): (transmembrane protein 91) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle and membrane. [provided by Alliance of Genome Resources, Apr 2022]
B9D2 (HGNC:28636): (B9 domain containing 2) This gene encodes a B9 domain protein, which are exclusively found in ciliated organisms. The gene is upregulated during mucociliary differentiation, and the encoded protein localizes to basal bodies and cilia. Disrupting expression of this gene results in ciliogenesis defects. [provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 19-41354391-A-G is Benign according to our data. Variant chr19-41354391-A-G is described in ClinVar as [Benign]. Clinvar id is 39302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
B9D2NM_030578.4 linkuse as main transcript downstream_gene_variant ENST00000243578.8
B9D2XM_011527349.3 linkuse as main transcript downstream_gene_variant
B9D2XM_011527350.3 linkuse as main transcript downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMEM91ENST00000539627.5 linkuse as main transcriptc.-30+3189A>G intron_variant 1
TMEM91ENST00000604123.5 linkuse as main transcriptc.142+76A>G intron_variant 3
B9D2ENST00000243578.8 linkuse as main transcript downstream_gene_variant 1 NM_030578.4 P1
B9D2ENST00000675972.1 linkuse as main transcript downstream_gene_variant P1

Frequencies

GnomAD3 genomes
AF:
0.687
AC:
104346
AN:
151848
Hom.:
36420
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.763
Gnomad AMI
AF:
0.816
Gnomad AMR
AF:
0.571
Gnomad ASJ
AF:
0.545
Gnomad EAS
AF:
0.445
Gnomad SAS
AF:
0.621
Gnomad FIN
AF:
0.744
Gnomad MID
AF:
0.608
Gnomad NFE
AF:
0.688
Gnomad OTH
AF:
0.644
GnomAD4 exome
AF:
0.659
AC:
288820
AN:
438204
Hom.:
96677
Cov.:
2
AF XY:
0.655
AC XY:
150231
AN XY:
229484
show subpopulations
Gnomad4 AFR exome
AF:
0.758
Gnomad4 AMR exome
AF:
0.545
Gnomad4 ASJ exome
AF:
0.534
Gnomad4 EAS exome
AF:
0.486
Gnomad4 SAS exome
AF:
0.619
Gnomad4 FIN exome
AF:
0.754
Gnomad4 NFE exome
AF:
0.687
Gnomad4 OTH exome
AF:
0.650
GnomAD4 genome
AF:
0.687
AC:
104435
AN:
151966
Hom.:
36451
Cov.:
31
AF XY:
0.684
AC XY:
50765
AN XY:
74256
show subpopulations
Gnomad4 AFR
AF:
0.763
Gnomad4 AMR
AF:
0.571
Gnomad4 ASJ
AF:
0.545
Gnomad4 EAS
AF:
0.445
Gnomad4 SAS
AF:
0.622
Gnomad4 FIN
AF:
0.744
Gnomad4 NFE
AF:
0.688
Gnomad4 OTH
AF:
0.642
Alfa
AF:
0.673
Hom.:
62689
Bravo
AF:
0.677
Asia WGS
AF:
0.548
AC:
1904
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 30, 2020This variant is associated with the following publications: (PMID: 23703862, 15175276, 21761116, 22282866, 16207846, 21679448, 18670143, 19536820, 16896927, 17333284, 9887336, 19614955, 18547814, 20232138, 14597484, 19096005) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
Cadd
Benign
2.6
Dann
Benign
0.48

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.

Other links and lift over

dbSNP: rs1800469; hg19: chr19-41860296; API