rs2273

Positions:

• chr4-75968235-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDAD1	NM_018115.4	c.988-901G>A		intron_variant		ENST00000356260.10	NP_060585.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDAD1	ENST00000356260.10	c.988-901G>A		intron_variant		1	NM_018115.4	ENSP00000348596	P1

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

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.0683

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.317

Alfa AF: 0.366 Hom.: 12839

Bravo AF: 0.304

Asia WGS AF: 0.266 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.8
DANN	Benign	0.70

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: rs2273; hg19: chr4-76889388;