chr4-75957574-G-C

Variant names:

• chr4-75957574-G-C
• rs2242472
• NM_018115.4:c.1713C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_018115.4(SDAD1):​c.1713C>G​(p.Ala571Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,614,092 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (37 hom.)
• Consequence: SDAD1 NM_018115.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650
• 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 4-75957574-G-C is Benign according to our data. Variant chr4-75957574-G-C is described in ClinVar as Benign. ClinVar VariationId is 773696.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.065 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00187 (285/152200) while in subpopulation EAS AF = 0.0482 (250/5182). AF 95% confidence interval is 0.0433. There are 7 homozygotes in GnomAd4. There are 163 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDAD1	NM_018115.4	MANE Select	c.1713C>G	p.Ala571Ala	synonymous	Exon 19 of 22	NP_060585.2	Q9NVU7-1
	SDAD1	NM_001288983.2		c.1602C>G	p.Ala534Ala	synonymous	Exon 18 of 21	NP_001275912.1	E7EW05
	SDAD1	NM_001288984.2		c.1422C>G	p.Ala474Ala	synonymous	Exon 19 of 22	NP_001275913.1	Q9NVU7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDAD1	ENST00000356260.10	TSL:1 MANE Select	c.1713C>G	p.Ala571Ala	synonymous	Exon 19 of 22	ENSP00000348596.5	Q9NVU7-1
	SDAD1	ENST00000395710.5	TSL:1	n.*1569C>G		non_coding_transcript_exon	Exon 19 of 22	ENSP00000379060.1	F8W8T7
	SDAD1	ENST00000395710.5	TSL:1	n.*1569C>G		3_prime_UTR	Exon 19 of 22	ENSP00000379060.1	F8W8T7

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 288 AN: 152082 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0485

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00336 AC: 846 AN: 251456 AF XY: 0.00327

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0422

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00136 AC: 1981 AN: 1461892 Hom.: 37 Cov.: 35 AF XY: 0.00138 AC XY: 1006 AN XY: 727248

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44724

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

East Asian (EAS) AF: 0.0400 AC: 1589 AN: 39700

South Asian (SAS) AF: 0.00121 AC: 104 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000890 AC: 99 AN: 1112012

Other (OTH) AF: 0.00296 AC: 179 AN: 60396

GnomAD4 genome AF: 0.00187 AC: 285 AN: 152200 Hom.: 7 Cov.: 32 AF XY: 0.00219 AC XY: 163 AN XY: 74406

African (AFR) AF: 0.0000723 AC: 3 AN: 41512

American (AMR) AF: 0.000261 AC: 4 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0482 AC: 250 AN: 5182

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68016

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.000424 Hom.: 0

Bravo AF: 0.00179

Asia WGS AF: 0.0150 AC: 52 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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	-0.46
CADD	Benign	7.1
DANN	Benign	0.59
PhyloP100		0.065
Mutation Taster		=99/1	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: rs2242472; hg19: chr4-76878727;