19-41363851-C-T

Variant names:

• chr19-41363851-C-T
• rs2241712
• NM_030578.4:c.-5+107G>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.-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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.46
• Publications: 44 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=-0.75).
• BP6: Variant 19-41363851-C-T is Benign according to our data. Variant chr19-41363851-C-T is described in ClinVar as Benign. ClinVar VariationId is 1167460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
B9D2	NM_030578.4	c.-5+107G>A		intron_variant	Intron 1 of 3	ENST00000243578.8	NP_085055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B9D2	ENST00000243578.8	c.-5+107G>A		intron_variant	Intron 1 of 3	1	NM_030578.4	ENSP00000243578.2

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

African (AFR) AF: 0.827 AC: 8552 AN: 10338

American (AMR) AF: 0.541 AC: 8231 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 5719 AN: 10874

East Asian (EAS) AF: 0.474 AC: 11212 AN: 23640

South Asian (SAS) AF: 0.608 AC: 25743 AN: 42342

European-Finnish (FIN) AF: 0.722 AC: 18046 AN: 24982

Middle Eastern (MID) AF: 0.587 AC: 927 AN: 1578

European-Non Finnish (NFE) AF: 0.679 AC: 150471 AN: 221690

Other (OTH) AF: 0.645 AC: 13483 AN: 20904

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

African (AFR) AF: 0.832 AC: 34583 AN: 41546

American (AMR) AF: 0.580 AC: 8866 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1869 AN: 3472

East Asian (EAS) AF: 0.443 AC: 2295 AN: 5178

South Asian (SAS) AF: 0.614 AC: 2961 AN: 4822

European-Finnish (FIN) AF: 0.716 AC: 7590 AN: 10594

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46488 AN: 67966

Other (OTH) AF: 0.650 AC: 1372 AN: 2112

Alfa AF: 0.695 Hom.: 13049

Bravo AF: 0.698

Asia WGS AF: 0.551 AC: 1912 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.75
CADD	Benign	0.089
DANN	Benign	0.80
PhyloP100		-4.5
PromoterAI		0.10	Neutral
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: rs2241712; hg19: chr19-41869756; COSMIC: COSV54683722; COSMIC: COSV54683722;