chr10-44995923-T-C

Variant names:

• chr10-44995923-T-C
• rs2297492
• XM_047426129.1:c.273+982T>C

Variant summary

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

The NR_126421.2(ZNF22-AS1):​n.512-1717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 152,142 control chromosomes in the GnomAD database, including 730 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 0.087 (730 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF22-AS1 NR_126421.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 6 publications found

Genes affected

LOC124902530 (HGNC:):

ZNF22-AS1 (HGNC:23509): (ZNF22 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

RASSF4 (HGNC:20793): (Ras association domain family member 4) The function of this gene has not yet been determined but may involve a role in tumor suppression. Alternative splicing of this gene results in several transcript variants; however, most of the variants have not been fully described. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_126421.2. 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
	ZNF22-AS1	NR_126421.2		n.512-1717A>G		intron	N/A
	RASSF4	NM_032023.4	MANE Select	c.*2594T>C		downstream_gene	N/A	NP_114412.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASSF4	ENST00000340258.10	TSL:1 MANE Select	c.*2594T>C		downstream_gene	N/A	ENSP00000339692.4

Frequencies

GnomAD3 genomes AF: 0.0872 AC: 13254 AN: 152024 Hom.: 731 Cov.: 32

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.0661

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0987

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.101

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0871 AC: 13252 AN: 152142 Hom.: 730 Cov.: 32 AF XY: 0.0892 AC XY: 6634 AN XY: 74358

African (AFR) AF: 0.0373 AC: 1551 AN: 41528

American (AMR) AF: 0.0905 AC: 1384 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 331 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1304 AN: 5156

South Asian (SAS) AF: 0.119 AC: 571 AN: 4812

European-Finnish (FIN) AF: 0.0987 AC: 1046 AN: 10594

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0992 AC: 6744 AN: 67970

Other (OTH) AF: 0.0995 AC: 210 AN: 2110

Alfa AF: 0.0946 Hom.: 1600

Bravo AF: 0.0848

Asia WGS AF: 0.153 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.1
DANN	Benign	0.72
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs2297492; hg19: chr10-45491371;