rs1800468

Positions:

• chr19-41354682-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id is 261879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-41354682-C-T is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
B9D2	NM_030578.4	c.*18G>A		3_prime_UTR_variant	4/4	ENST00000243578.8	NP_085055.2
B9D2	XM_011527349.3	c.*18G>A		3_prime_UTR_variant	4/4		XP_011525651.1
B9D2	XM_011527350.3	c.*18G>A		3_prime_UTR_variant	3/3		XP_011525652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
B9D2	ENST00000243578.8	c.*18G>A		3_prime_UTR_variant	4/4	1	NM_030578.4	ENSP00000243578	P1

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

GnomAD3 exomes AF: 0.0622 AC: 15532 AN: 249712 Hom.: 567 AF XY: 0.0642 AC XY: 8681 AN XY: 135236

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 SAS exome AF: 0.0682

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

Gnomad4 AFR exome AF: 0.0278

Gnomad4 AMR exome AF: 0.0422

Gnomad4 ASJ exome AF: 0.0712

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.0676

Gnomad4 FIN exome AF: 0.0517

Gnomad4 NFE exome AF: 0.0846

Gnomad4 OTH exome AF: 0.0753

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

Gnomad4 AFR AF: 0.0283

Gnomad4 AMR AF: 0.0631

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0637

Gnomad4 FIN AF: 0.0489

Gnomad4 NFE AF: 0.0810

Gnomad4 OTH AF: 0.0554

Alfa AF: 0.0737 Hom.: 140

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 9887336) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 11, 2023

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Meckel syndrome, type 10 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800468; hg19: chr19-41860587;