chr7-66988413-G-A

Variant names:

• chr7-66988413-G-A
• rs146166884
• NM_016038.4:c.711C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_016038.4(SBDS):​c.711C>T​(p.Leu237Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: SBDS NM_016038.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.09
• Publications: 1 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: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 7-66988413-G-A is Benign according to our data. Variant chr7-66988413-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2451811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.09 with no splicing effect.

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.711C>T	p.Leu237Leu	synonymous	Exon 5 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.711C>T	p.Leu237Leu	synonymous	Exon 5 of 5	ENSP00000246868.2	Q9Y3A5
	SBDS	ENST00000697897.1		c.711C>T	p.Leu237Leu	synonymous	Exon 6 of 6	ENSP00000513469.1	Q9Y3A5
	SBDS	ENST00000890817.1		c.711C>T	p.Leu237Leu	synonymous	Exon 6 of 6	ENSP00000560876.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251334 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000703

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000616 AC: 90 AN: 1461484 Hom.: 0 Cov.: 31 AF XY: 0.0000633 AC XY: 46 AN XY: 727090

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000782 AC: 87 AN: 1111924

Other (OTH) AF: 0.0000497 AC: 3 AN: 60392

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.0000656 AC: 1 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000948 Hom.: 0

Bravo AF: 0.0000151

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Benign	0.77
PhyloP100		3.1

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: rs146166884; hg19: chr7-66453400; COSMIC: COSV55887136; COSMIC: COSV55887136;