rs186000847

chr7-66994193-T-Cchr7-66994193-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016038.4(SBDS):c.258+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,204 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (18 hom., cov: 31)
  • Exomes 𝑓: 0.014 (178 hom.)
• Consequence: SBDS NM_016038.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.33

Genes affected

SBDS (HGNC:19440): (SBDS ribosome maturation factor) This gene encodes a highly conserved protein that plays an essential role in ribosome biogenesis. The encoded protein interacts with elongation factor-like GTPase 1 to disassociate eukaryotic initiation factor 6 from the late cytoplasmic pre-60S ribosomal subunit allowing assembly of the 80S subunit. Mutations within this gene are associated with the autosomal recessive disorder Shwachman-Bodian-Diamond syndrome. This gene has a closely linked pseudogene that is distally located. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-66994193-T-C is Benign according to our data. Variant chr7-66994193-T-C is described in ClinVar as [Benign]. Clinvar id is 260684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-66994193-T-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0109 (1654/152260) while in subpopulation NFE AF= 0.0174 (1186/68018). AF 95% confidence interval is 0.0166. There are 18 homozygotes in gnomad4. There are 793 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBDS	NM_016038.4	c.258+19A>G		intron_variant		ENST00000246868.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBDS	ENST00000246868.7	c.258+19A>G		intron_variant		1	NM_016038.4	P1

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1653 AN: 152142 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.00328

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.0109 AC: 2729 AN: 251378 Hom.: 24 AF XY: 0.0107 AC XY: 1450 AN XY: 135874

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00451

Gnomad ASJ exome AF: 0.0215

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00206

Gnomad FIN exome AF: 0.0185

Gnomad NFE exome AF: 0.0158

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0141 AC: 20646 AN: 1460944 Hom.: 178 Cov.: 32 AF XY: 0.0138 AC XY: 10017 AN XY: 726816

Gnomad4 AFR exome AF: 0.00188

Gnomad4 AMR exome AF: 0.00416

Gnomad4 ASJ exome AF: 0.0199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00249

Gnomad4 FIN exome AF: 0.0199

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0112

GnomAD4 genome AF: 0.0109 AC: 1654 AN: 152260 Hom.: 18 Cov.: 31 AF XY: 0.0107 AC XY: 793 AN XY: 74430

Gnomad4 AFR AF: 0.00253

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0176

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.0181 Hom.: 5

Bravo AF: 0.00917

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Shwachman-Diamond syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.049
Dann	Benign	0.63

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: rs186000847; hg19: chr7-66459180; COSMIC: COSV55888886; COSMIC: COSV55888886;