rs1061695

Variant names:

• chr7-66994269-T-C
• rs1061695
• NM_016038.4:c.201A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016038.4(SBDS):​c.201A>G​(p.Lys67Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 1,611,710 control chromosomes in the GnomAD database, including 9,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (772 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8545 hom.)
• Consequence: SBDS NM_016038.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.61
• Publications: 20 publications found

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]

SBDS Gene-Disease associations (from GenCC):

• Shwachman-Diamond syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Shwachman-Diamond syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 7-66994269-T-C is Benign according to our data. Variant chr7-66994269-T-C is described in ClinVar as Benign. ClinVar VariationId is 21537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016038.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBDS	NM_016038.4	MANE Select	c.201A>G	p.Lys67Lys	synonymous	Exon 2 of 5	NP_057122.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBDS	ENST00000246868.7	TSL:1 MANE Select	c.201A>G	p.Lys67Lys	synonymous	Exon 2 of 5	ENSP00000246868.2
	SBDS	ENST00000697897.1		c.201A>G	p.Lys67Lys	synonymous	Exon 3 of 6	ENSP00000513469.1
	SBDS	ENST00000890817.1		c.201A>G	p.Lys67Lys	synonymous	Exon 3 of 6	ENSP00000560876.1

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12866 AN: 152056 Hom.: 771 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0853

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.0874 AC: 21958 AN: 251294 AF XY: 0.0873

Gnomad AFR exome AF: 0.0233

Gnomad AMR exome AF: 0.0601

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.00321

Gnomad FIN exome AF: 0.215

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.0987

GnomAD4 exome AF: 0.101 AC: 147396 AN: 1459538 Hom.: 8545 Cov.: 32 AF XY: 0.0991 AC XY: 71949 AN XY: 726206

African (AFR) AF: 0.0207 AC: 694 AN: 33452

American (AMR) AF: 0.0627 AC: 2801 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2733 AN: 26122

East Asian (EAS) AF: 0.00247 AC: 98 AN: 39664

South Asian (SAS) AF: 0.0359 AC: 3092 AN: 86208

European-Finnish (FIN) AF: 0.209 AC: 11145 AN: 53390

Middle Eastern (MID) AF: 0.0699 AC: 403 AN: 5762

European-Non Finnish (NFE) AF: 0.109 AC: 120919 AN: 1109918

Other (OTH) AF: 0.0913 AC: 5511 AN: 60334

GnomAD4 genome AF: 0.0846 AC: 12868 AN: 152172 Hom.: 772 Cov.: 32 AF XY: 0.0881 AC XY: 6553 AN XY: 74388

African (AFR) AF: 0.0261 AC: 1085 AN: 41546

American (AMR) AF: 0.0852 AC: 1302 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3472

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5178

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4824

European-Finnish (FIN) AF: 0.220 AC: 2327 AN: 10572

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7342 AN: 67976

Other (OTH) AF: 0.0991 AC: 209 AN: 2108

Alfa AF: 0.0941 Hom.: 676

Bravo AF: 0.0731

Asia WGS AF: 0.0180 AC: 65 AN: 3478

EpiCase AF: 0.108

EpiControl AF: 0.103

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	2	Shwachman-Diamond syndrome 1 (2)
-	-	1	Aplastic anemia (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1061695; hg19: chr7-66459256; COSMIC: COSV55887570; COSMIC: COSV55887570;