rs737923

Variant names:

• chr22-19144812-A-G
• rs737923
• NM_022719.3:c.-172T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-19144812-A-G
• chr22-19144812-A-T

Variant summary

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

The NM_022719.3(ESS2):​c.-172T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,073,982 control chromosomes in the GnomAD database, including 81,214 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 0.41 (13432 hom., cov: 32)
  • Exomes 𝑓: 0.37 (67782 hom.)
• Consequence: ESS2 NM_022719.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 14 publications found

Genes affected

ESS2 (HGNC:16817): (ess-2 splicing factor homolog) This gene is located within the minimal DGS critical region (MDGCR) thought to contain the gene(s) responsible for a group of developmental disorders. These disorders include DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and some familial or sporadic conotruncal cardiac defects which have been associated with microdeletion of 22q11.2. The encoded protein may be a component of C complex spliceosomes, and the orthologous protein in the mouse localizes to the nucleus. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022719.3. 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
	ESS2	NM_022719.3	MANE Select	c.-172T>C		upstream_gene	N/A	NP_073210.1
	ESS2	NR_134304.2		n.-161T>C		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESS2	ENST00000252137.11	TSL:1 MANE Select	c.-172T>C		upstream_gene	N/A	ENSP00000252137.6
	ESS2	ENST00000951416.1		c.-172T>C		upstream_gene	N/A	ENSP00000621475.1
	ESS2	ENST00000909110.1		c.-172T>C		upstream_gene	N/A	ENSP00000579169.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62734 AN: 151970 Hom.: 13390 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.375 AC: 345385 AN: 921894 Hom.: 67782 AF XY: 0.377 AC XY: 170305 AN XY: 451982

African (AFR) AF: 0.464 AC: 8697 AN: 18724

American (AMR) AF: 0.393 AC: 4616 AN: 11734

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 5653 AN: 14930

East Asian (EAS) AF: 0.736 AC: 19462 AN: 26442

South Asian (SAS) AF: 0.459 AC: 19368 AN: 42188

European-Finnish (FIN) AF: 0.390 AC: 10796 AN: 27698

Middle Eastern (MID) AF: 0.379 AC: 1053 AN: 2778

European-Non Finnish (NFE) AF: 0.353 AC: 260297 AN: 737838

Other (OTH) AF: 0.390 AC: 15443 AN: 39562

GnomAD4 genome AF: 0.413 AC: 62838 AN: 152088 Hom.: 13432 Cov.: 32 AF XY: 0.419 AC XY: 31123 AN XY: 74340

African (AFR) AF: 0.461 AC: 19139 AN: 41494

American (AMR) AF: 0.417 AC: 6366 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1321 AN: 3472

East Asian (EAS) AF: 0.690 AC: 3558 AN: 5156

South Asian (SAS) AF: 0.491 AC: 2370 AN: 4826

European-Finnish (FIN) AF: 0.404 AC: 4268 AN: 10566

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24647 AN: 67978

Other (OTH) AF: 0.411 AC: 865 AN: 2106

Alfa AF: 0.381 Hom.: 30701

Bravo AF: 0.412

Asia WGS AF: 0.596 AC: 2071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.56
DANN	Benign	0.75
PhyloP100		-1.5
PromoterAI		-0.081	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs737923; hg19: chr22-19132325;