chr4-75982032-T-C

Variant names:

• chr4-75982032-T-C
• rs117413297
• NM_018115.4:c.96A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001288984.2(SDAD1):​c.-271A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,595,420 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (43 hom.)
• Consequence: SDAD1 NM_001288984.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.300
• Publications: 3 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]

SDAD1-AS1 (HGNC:41106): (SDAD1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 4-75982032-T-C is Benign according to our data. Variant chr4-75982032-T-C is described in ClinVar as Benign. ClinVar VariationId is 729521.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00181 (275/152354) while in subpopulation EAS AF = 0.0459 (238/5190). AF 95% confidence interval is 0.0411. There are 6 homozygotes in GnomAd4. There are 167 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001288984.2. 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
	SDAD1	NM_018115.4	MANE Select	c.96A>G	p.Leu32Leu	synonymous	Exon 2 of 22	NP_060585.2	Q9NVU7-1
	SDAD1	NM_001288984.2		c.-271A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 22	NP_001275913.1	Q9NVU7-2
	SDAD1	NM_001288983.2		c.96A>G	p.Leu32Leu	synonymous	Exon 2 of 21	NP_001275912.1	E7EW05

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDAD1	ENST00000356260.10	TSL:1 MANE Select	c.96A>G	p.Leu32Leu	synonymous	Exon 2 of 22	ENSP00000348596.5	Q9NVU7-1
	SDAD1	ENST00000395710.5	TSL:1	n.96A>G		non_coding_transcript_exon	Exon 2 of 22	ENSP00000379060.1	F8W8T7
	SDAD1-AS1	ENST00000501239.2	TSL:1	n.176+1067T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 275 AN: 152234 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00635

Gnomad EAS AF: 0.0458

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00363 AC: 885 AN: 243744 AF XY: 0.00354

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00389

Gnomad EAS exome AF: 0.0449

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.00135

GnomAD4 exome AF: 0.00129 AC: 1868 AN: 1443066 Hom.: 43 Cov.: 27 AF XY: 0.00125 AC XY: 899 AN XY: 718454

African (AFR) AF: 0.00 AC: 0 AN: 32814

American (AMR) AF: 0.0000236 AC: 1 AN: 42430

Ashkenazi Jewish (ASJ) AF: 0.00420 AC: 108 AN: 25734

East Asian (EAS) AF: 0.0393 AC: 1551 AN: 39440

South Asian (SAS) AF: 0.000393 AC: 33 AN: 83888

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53204

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5680

European-Non Finnish (NFE) AF: 0.0000709 AC: 78 AN: 1100178

Other (OTH) AF: 0.00159 AC: 95 AN: 59698

GnomAD4 genome AF: 0.00181 AC: 275 AN: 152354 Hom.: 6 Cov.: 32 AF XY: 0.00224 AC XY: 167 AN XY: 74510

African (AFR) AF: 0.00 AC: 0 AN: 41596

American (AMR) AF: 0.000196 AC: 3 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00635 AC: 22 AN: 3466

East Asian (EAS) AF: 0.0459 AC: 238 AN: 5190

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000542 Hom.: 2

Bravo AF: 0.00263

Asia WGS AF: 0.00868 AC: 30 AN: 3472

EpiCase AF: 0.000219

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.8
DANN	Benign	0.83
PhyloP100		-0.30
Mutation Taster		=94/6	polymorphism

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: rs117413297; hg19: chr4-76903185; COSMIC: COSV62403286; COSMIC: COSV62403286;