19-41355769-C-T

Variant names:

• chr19-41355769-C-T
• rs2317130
• NM_030578.4:c.215-756G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030578.4(B9D2):​c.215-756G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,096 control chromosomes in the GnomAD database, including 34,382 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 0.67 (34382 hom., cov: 32)
• Consequence: B9D2 NM_030578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 26 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B9D2	NM_030578.4	c.215-756G>A		intron_variant	Intron 3 of 3	ENST00000243578.8	NP_085055.2
B9D2	XM_011527349.3	c.215-756G>A		intron_variant	Intron 3 of 3		XP_011525651.1
B9D2	XM_011527350.3	c.56-756G>A		intron_variant	Intron 2 of 2		XP_011525652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B9D2	ENST00000243578.8	c.215-756G>A		intron_variant	Intron 3 of 3	1	NM_030578.4	ENSP00000243578.2

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101527 AN: 151976 Hom.: 34366 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.668 AC: 101589 AN: 152096 Hom.: 34382 Cov.: 32 AF XY: 0.664 AC XY: 49380 AN XY: 74348

African (AFR) AF: 0.711 AC: 29509 AN: 41484

American (AMR) AF: 0.564 AC: 8621 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1874 AN: 3472

East Asian (EAS) AF: 0.447 AC: 2314 AN: 5174

South Asian (SAS) AF: 0.614 AC: 2956 AN: 4816

European-Finnish (FIN) AF: 0.716 AC: 7570 AN: 10568

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46503 AN: 67990

Other (OTH) AF: 0.627 AC: 1325 AN: 2112

Alfa AF: 0.663 Hom.: 9164

Bravo AF: 0.658

Asia WGS AF: 0.538 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2317130; hg19: chr19-41861674;