rs2241712

chr19-41363851-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030578.4(B9D2):c.-5+107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 523,738 control chromosomes in the GnomAD database, including 118,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.70 (38420 hom., cov: 34)
  • Exomes 𝑓: 0.65 (80475 hom.)
• Consequence: B9D2 NM_030578.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.46

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 19-41363851-C-T is Benign according to our data. Variant chr19-41363851-C-T is described in ClinVar as [Benign]. Clinvar id is 1167460.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B9D2	NM_030578.4	c.-5+107G>A		intron_variant		ENST00000243578.8
B9D2	XM_011527349.3	c.-92G>A		5_prime_UTR_variant	1/4
B9D2	XM_011527350.3	c.-72+107G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B9D2	ENST00000243578.8	c.-5+107G>A		intron_variant		1	NM_030578.4	P1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106845 AN: 152064 Hom.: 38383 Cov.: 34

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.652

GnomAD4 exome AF: 0.652 AC: 242384 AN: 371554 Hom.: 80475 AF XY: 0.647 AC XY: 127464 AN XY: 197034

Gnomad4 AFR exome AF: 0.827

Gnomad4 AMR exome AF: 0.541

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.474

Gnomad4 SAS exome AF: 0.608

Gnomad4 FIN exome AF: 0.722

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.645

GnomAD4 genome AF: 0.703 AC: 106943 AN: 152184 Hom.: 38420 Cov.: 34 AF XY: 0.697 AC XY: 51852 AN XY: 74398

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.650

Alfa AF: 0.702 Hom.: 8125

Bravo AF: 0.698

Asia WGS AF: 0.551 AC: 1912 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.089
Dann	Benign	0.80

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: rs2241712; hg19: chr19-41869756; COSMIC: COSV54683722; COSMIC: COSV54683722;