rs2273

Variant names:

• chr4-75968235-C-T
• rs2273
• NM_018115.4:c.988-901G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018115.4(SDAD1):​c.988-901G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,046 control chromosomes in the GnomAD database, including 9,165 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (9165 hom., cov: 32)
• Consequence: SDAD1 NM_018115.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406
• Publications: 37 publications found

Genes affected

SDAD1 (HGNC:25537): (SDA1 domain containing 1) Predicted to be involved in ribosomal large subunit biogenesis and ribosomal large subunit export from nucleus. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018115.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDAD1	NM_018115.4	MANE Select	c.988-901G>A		intron	N/A	NP_060585.2
	SDAD1	NM_001288983.2		c.877-901G>A		intron	N/A	NP_001275912.1
	SDAD1	NM_001288984.2		c.697-901G>A		intron	N/A	NP_001275913.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDAD1	ENST00000356260.10	TSL:1 MANE Select	c.988-901G>A		intron	N/A	ENSP00000348596.5
	SDAD1	ENST00000395710.5	TSL:1	n.*844-901G>A		intron	N/A	ENSP00000379060.1
	SDAD1	ENST00000395711.8	TSL:2	c.877-901G>A		intron	N/A	ENSP00000379061.4

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50298 AN: 151928 Hom.: 9172 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.317

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.331 AC: 50290 AN: 152046 Hom.: 9165 Cov.: 32 AF XY: 0.331 AC XY: 24592 AN XY: 74318

African (AFR) AF: 0.252 AC: 10467 AN: 41478

American (AMR) AF: 0.231 AC: 3530 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3466

East Asian (EAS) AF: 0.0683 AC: 354 AN: 5182

South Asian (SAS) AF: 0.424 AC: 2045 AN: 4822

European-Finnish (FIN) AF: 0.451 AC: 4760 AN: 10546

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26949 AN: 67950

Other (OTH) AF: 0.317 AC: 668 AN: 2110

Alfa AF: 0.361 Hom.: 31826

Bravo AF: 0.304

Asia WGS AF: 0.266 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.8
DANN	Benign	0.70
PhyloP100		0.41
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: rs2273; hg19: chr4-76889388;