rs3087453

Variant names:

• chr19-41355029-G-C
• rs3087453
• NM_030578.4:c.215-16C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-41355029-G-C
• chr19-41355029-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030578.4(B9D2):​c.215-16C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,569,160 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (33 hom.)
• Consequence: B9D2 NM_030578.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.878
• Publications: 4 publications found

Genes affected

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]

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:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-41355029-G-C is Benign according to our data. Variant chr19-41355029-G-C is described in ClinVar as Benign. ClinVar VariationId is 261880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0125 (1899/152278) while in subpopulation AFR AF = 0.0427 (1774/41532). AF 95% confidence interval is 0.0411. There are 40 homozygotes in GnomAd4. There are 928 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 40 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030578.4. 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.215-16C>G		intron	N/A	NP_085055.2	Q9BPU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B9D2	ENST00000243578.8	TSL:1 MANE Select	c.215-16C>G		intron	N/A	ENSP00000243578.2	Q9BPU9
	TMEM91	ENST00000539627.5	TSL:1	c.-30+3827G>C		intron	N/A	ENSP00000441900.1	F5GWC9
	TMEM91	ENST00000604123.5	TSL:3	c.142+714G>C		intron	N/A	ENSP00000474871.1	S4R3Y8

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1894 AN: 152160 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00301 AC: 560 AN: 186078 AF XY: 0.00225

Gnomad AFR exome AF: 0.0421

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.000146

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000190

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00124 AC: 1758 AN: 1416882 Hom.: 33 Cov.: 32 AF XY: 0.00105 AC XY: 735 AN XY: 699814

African (AFR) AF: 0.0423 AC: 1371 AN: 32428

American (AMR) AF: 0.00225 AC: 91 AN: 40392

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 7 AN: 23794

East Asian (EAS) AF: 0.00 AC: 0 AN: 38284

South Asian (SAS) AF: 0.0000250 AC: 2 AN: 80078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50364

Middle Eastern (MID) AF: 0.00181 AC: 10 AN: 5514

European-Non Finnish (NFE) AF: 0.000119 AC: 129 AN: 1087522

Other (OTH) AF: 0.00253 AC: 148 AN: 58506

GnomAD4 genome AF: 0.0125 AC: 1899 AN: 152278 Hom.: 40 Cov.: 32 AF XY: 0.0125 AC XY: 928 AN XY: 74456

African (AFR) AF: 0.0427 AC: 1774 AN: 41532

American (AMR) AF: 0.00601 AC: 92 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68028

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00659 Hom.: 4

Bravo AF: 0.0142

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.53
DANN	Benign	0.68
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3087453; hg19: chr19-41860934;