rs1800468

Variant names:

• chr19-41354682-C-T
• rs1800468
• NM_030578.4:c.*18G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030578.4(B9D2):​c.*18G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 1,613,668 control chromosomes in the GnomAD database, including 5,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (319 hom., cov: 32)
  • Exomes 𝑓: 0.077 (4742 hom.)
• Consequence: B9D2 NM_030578.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.133
• Publications: 168 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 19-41354682-C-T is Benign according to our data. Variant chr19-41354682-C-T is described in ClinVar as Benign. ClinVar VariationId is 261879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B9D2	NM_030578.4	c.*18G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000243578.8	NP_085055.2
B9D2	XM_011527349.3	c.*18G>A		3_prime_UTR_variant	Exon 4 of 4		XP_011525651.1
B9D2	XM_011527350.3	c.*18G>A		3_prime_UTR_variant	Exon 3 of 3		XP_011525652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B9D2	ENST00000243578.8	c.*18G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_030578.4	ENSP00000243578.2

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 8998 AN: 152088 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0633

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.0489

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.0560

GnomAD2 exomes AF: 0.0622 AC: 15532 AN: 249712 AF XY: 0.0642

Gnomad AFR exome AF: 0.0289

Gnomad AMR exome AF: 0.0407

Gnomad ASJ exome AF: 0.0731

Gnomad EAS exome AF: 0.000436

Gnomad FIN exome AF: 0.0527

Gnomad NFE exome AF: 0.0827

Gnomad OTH exome AF: 0.0648

GnomAD4 exome AF: 0.0770 AC: 112467 AN: 1461462 Hom.: 4742 Cov.: 32 AF XY: 0.0772 AC XY: 56119 AN XY: 727032

African (AFR) AF: 0.0278 AC: 931 AN: 33480

American (AMR) AF: 0.0422 AC: 1887 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 1861 AN: 26136

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39700

South Asian (SAS) AF: 0.0676 AC: 5830 AN: 86250

European-Finnish (FIN) AF: 0.0517 AC: 2749 AN: 53222

Middle Eastern (MID) AF: 0.102 AC: 589 AN: 5768

European-Non Finnish (NFE) AF: 0.0846 AC: 94059 AN: 1111810

Other (OTH) AF: 0.0753 AC: 4547 AN: 60382

GnomAD4 genome AF: 0.0591 AC: 9000 AN: 152206 Hom.: 319 Cov.: 32 AF XY: 0.0578 AC XY: 4303 AN XY: 74406

African (AFR) AF: 0.0283 AC: 1175 AN: 41524

American (AMR) AF: 0.0631 AC: 965 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0637 AC: 307 AN: 4818

European-Finnish (FIN) AF: 0.0489 AC: 519 AN: 10614

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0810 AC: 5508 AN: 68004

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

Alfa AF: 0.0647 Hom.: 145

Bravo AF: 0.0588

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 9887336) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Meckel syndrome, type 10 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Meckel-Gruber syndrome;C0431399:Joubert syndrome Benign:1

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.57
PhyloP100		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs1800468; hg19: chr19-41860587;