rs4803457

Positions:

• chr19-41355454-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030578.4(B9D2):​c.215-441A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,938 control chromosomes in the GnomAD database, including 26,667 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 0.59 (26667 hom., cov: 32)
• Consequence: B9D2 NM_030578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B9D2	NM_030578.4	c.215-441A>G		intron_variant		ENST00000243578.8
B9D2	XM_011527349.3	c.215-441A>G		intron_variant
B9D2	XM_011527350.3	c.56-441A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B9D2	ENST00000243578.8	c.215-441A>G		intron_variant		1	NM_030578.4	P1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89335 AN: 151820 Hom.: 26666 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.588 AC: 89367 AN: 151938 Hom.: 26667 Cov.: 32 AF XY: 0.589 AC XY: 43698 AN XY: 74246

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.562

Alfa AF: 0.590 Hom.: 3860

Bravo AF: 0.573

Asia WGS AF: 0.502 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs4803457; hg19: chr19-41861359;