rs1800469

Positions:

• chr19-41354391-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.81

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]

ACMG classification

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	Protein	UniProt
B9D2	NM_030578.4			downstream_gene_variant		ENST00000243578.8	NP_085055.2
B9D2	XM_011527349.3			downstream_gene_variant			XP_011525651.1
B9D2	XM_011527350.3			downstream_gene_variant			XP_011525652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM91	ENST00000539627.5	c.-30+3189A>G		intron_variant		1		ENSP00000441900
TMEM91	ENST00000604123.5	c.142+76A>G		intron_variant		3		ENSP00000474871
B9D2	ENST00000243578.8			downstream_gene_variant		1	NM_030578.4	ENSP00000243578	P1
B9D2	ENST00000675972.1			downstream_gene_variant				ENSP00000501911	P1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104346 AN: 151848 Hom.: 36420 Cov.: 31

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

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

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2020	This variant is associated with the following publications: (PMID: 23703862, 15175276, 21761116, 22282866, 16207846, 21679448, 18670143, 19536820, 16896927, 17333284, 9887336, 19614955, 18547814, 20232138, 14597484, 19096005) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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

Other links and lift over

dbSNP: rs1800469; hg19: chr19-41860296;