rs34088631

chr19-41357916-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS1

The NM_030578.4(B9D2):c.195C>T(p.Phe65=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,614,138 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0026 (5 hom.)
• Consequence: B9D2 NM_030578.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.00100

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 19-41357916-G-A is Benign according to our data. Variant chr19-41357916-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-41357916-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.001 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00253 (386/152302) while in subpopulation AMR AF= 0.00543 (83/15292). AF 95% confidence interval is 0.00449. There are 1 homozygotes in gnomad4. There are 184 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
B9D2	NM_030578.4	c.195C>T	p.Phe65=	synonymous_variant	3/4	ENST00000243578.8
B9D2	XM_011527349.3	c.195C>T	p.Phe65=	synonymous_variant	3/4
B9D2	XM_011527350.3	c.36C>T	p.Phe12=	synonymous_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B9D2	ENST00000243578.8	c.195C>T	p.Phe65=	synonymous_variant	3/4	1	NM_030578.4	P1

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 386 AN: 152184 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00378

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00205 AC: 516 AN: 251374 Hom.: 0 AF XY: 0.00200 AC XY: 272 AN XY: 135868

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00356

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00263 AC: 3845 AN: 1461836 Hom.: 5 Cov.: 34 AF XY: 0.00259 AC XY: 1882 AN XY: 727218

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.00206

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.000524

Gnomad4 NFE exome AF: 0.00319

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00253 AC: 386 AN: 152302 Hom.: 1 Cov.: 31 AF XY: 0.00247 AC XY: 184 AN XY: 74458

Gnomad4 AFR AF: 0.000674

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00378

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00300 Hom.: 1

Bravo AF: 0.00281

EpiCase AF: 0.00322

EpiControl AF: 0.00403

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 05, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	B9D2: BP4, BP7 -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	6.3
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34088631; hg19: chr19-41863821; COSMIC: COSV99699214; COSMIC: COSV99699214;