rs60712404

Variant names:

• chr7-66995210-A-G
• rs60712404
• NM_016038.4:c.128+80T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-66995210-A-G
• chr7-66995210-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016038.4(SBDS):​c.128+80T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,591,180 control chromosomes in the GnomAD database, including 1,475 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (790 hom., cov: 33)
  • Exomes 𝑓: 0.0058 (685 hom.)
• Consequence: SBDS NM_016038.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.21
• Publications: 2 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]

TYW1 (HGNC:25598): (tRNA-yW synthesizing protein 1 homolog) Wybutosine (yW) is a hypermodified guanosine found in phenylalanine tRNA adjacent to the anticodon that stabilizes codon-anticodon interactions in the ribosome. In yeast, the homolog of this gene is essential for the synthesis of wybutosine. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 7-66995210-A-G is Benign according to our data. Variant chr7-66995210-A-G is described in ClinVar as [Benign]. Clinvar id is 1239540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBDS	NM_016038.4	c.128+80T>C		intron_variant	Intron 1 of 4	ENST00000246868.7	NP_057122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBDS	ENST00000246868.7	c.128+80T>C		intron_variant	Intron 1 of 4	1	NM_016038.4	ENSP00000246868.2

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8476 AN: 151884 Hom.: 790 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000971

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.00582 AC: 8377 AN: 1439178 Hom.: 685 Cov.: 28 AF XY: 0.00507 AC XY: 3635 AN XY: 716716

African (AFR) AF: 0.193 AC: 6395 AN: 33070

American (AMR) AF: 0.0117 AC: 522 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.00485 AC: 126 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.000420 AC: 36 AN: 85646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52948

Middle Eastern (MID) AF: 0.00875 AC: 38 AN: 4342

European-Non Finnish (NFE) AF: 0.000483 AC: 528 AN: 1093546

Other (OTH) AF: 0.0123 AC: 732 AN: 59484

GnomAD4 genome AF: 0.0558 AC: 8485 AN: 152002 Hom.: 790 Cov.: 33 AF XY: 0.0536 AC XY: 3979 AN XY: 74302

African (AFR) AF: 0.193 AC: 7987 AN: 41462

American (AMR) AF: 0.0214 AC: 326 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000971 AC: 66 AN: 67946

Other (OTH) AF: 0.0374 AC: 79 AN: 2112

Alfa AF: 0.0418 Hom.: 53

Bravo AF: 0.0626

Asia WGS AF: 0.0110 AC: 40 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

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	-0.80
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-1.2
PromoterAI		0.048	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: rs60712404; hg19: chr7-66460197;