rs1800469

Variant names:

• chr19-41354391-A-G
• rs1800469
• ENST00000539627.5:c.-30+3189A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-41354391-A-G
• chr19-41354391-A-C
• chr19-41354391-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 968 publications found

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]

ENSG00000255730 (HGNC:):

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]

B9D2 Gene-Disease associations (from GenCC):

• Meckel syndrome, type 10

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• ciliopathy

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000539627.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B9D2	NM_030578.4	MANE Select	c.*309T>C		downstream_gene	N/A	NP_085055.2	Q9BPU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM91	ENST00000539627.5	TSL:1	c.-30+3189A>G		intron	N/A	ENSP00000441900.1	F5GWC9
	TMEM91	ENST00000604123.5	TSL:3	c.142+76A>G		intron	N/A	ENSP00000474871.1	S4R3Y8
	TMEM91	ENST00000889861.1		c.-30+3189A>G		intron	N/A	ENSP00000559920.1

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

African (AFR) AF: 0.758 AC: 9307 AN: 12284

American (AMR) AF: 0.545 AC: 10039 AN: 18428

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 7190 AN: 13468

East Asian (EAS) AF: 0.486 AC: 14981 AN: 30828

South Asian (SAS) AF: 0.619 AC: 27060 AN: 43736

European-Finnish (FIN) AF: 0.754 AC: 22140 AN: 29364

Middle Eastern (MID) AF: 0.593 AC: 1133 AN: 1910

European-Non Finnish (NFE) AF: 0.687 AC: 180307 AN: 262568

Other (OTH) AF: 0.650 AC: 16663 AN: 25618

GnomAD4 genome AF: 0.687 AC: 104435 AN: 151966 Hom.: 36451 Cov.: 31 AF XY: 0.684 AC XY: 50765 AN XY: 74256

African (AFR) AF: 0.763 AC: 31626 AN: 41434

American (AMR) AF: 0.571 AC: 8726 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1890 AN: 3470

East Asian (EAS) AF: 0.445 AC: 2288 AN: 5136

South Asian (SAS) AF: 0.622 AC: 2995 AN: 4814

European-Finnish (FIN) AF: 0.744 AC: 7879 AN: 10592

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46756 AN: 67918

Other (OTH) AF: 0.642 AC: 1355 AN: 2110

Alfa AF: 0.681 Hom.: 141135

Bravo AF: 0.677

Asia WGS AF: 0.548 AC: 1904 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Meckel-Gruber syndrome;C5979921:Joubert syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.48
PhyloP100		-1.8
PromoterAI		0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1800469; hg19: chr19-41860296;