9-114007235-C-T

Variant names:

• chr9-114007235-C-T
• rs4979321
• NM_001318042.2:c.551-115C>T

Variant summary

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

The NM_001318042.2(ZNF618):​c.551-115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 801,416 control chromosomes in the GnomAD database, including 159,434 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 0.55 (24938 hom., cov: 31)
  • Exomes 𝑓: 0.64 (134496 hom.)
• Consequence: ZNF618 NM_001318042.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 5 publications found

Genes affected

ZNF618 (HGNC:29416): (zinc finger protein 618) Enables identical protein binding activity and transcription coregulator binding activity. Involved in positive regulation of chromatin binding activity. Located in chromatin. Part of pericentric heterochromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF618	NM_001318042.2	c.551-115C>T		intron_variant	Intron 6 of 14	ENST00000374126.10	NP_001304971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF618	ENST00000374126.10	c.551-115C>T		intron_variant	Intron 6 of 14	1	NM_001318042.2	ENSP00000363241.5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83337 AN: 151878 Hom.: 24936 Cov.: 31

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.639 AC: 415050 AN: 649420 Hom.: 134496 AF XY: 0.640 AC XY: 215847 AN XY: 337356

African (AFR) AF: 0.281 AC: 4577 AN: 16316

American (AMR) AF: 0.556 AC: 14287 AN: 25678

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 10551 AN: 16380

East Asian (EAS) AF: 0.674 AC: 21316 AN: 31606

South Asian (SAS) AF: 0.620 AC: 32474 AN: 52338

European-Finnish (FIN) AF: 0.713 AC: 27574 AN: 38696

Middle Eastern (MID) AF: 0.512 AC: 2054 AN: 4010

European-Non Finnish (NFE) AF: 0.654 AC: 282303 AN: 431456

Other (OTH) AF: 0.605 AC: 19914 AN: 32940

GnomAD4 genome AF: 0.548 AC: 83357 AN: 151996 Hom.: 24938 Cov.: 31 AF XY: 0.551 AC XY: 40966 AN XY: 74300

African (AFR) AF: 0.293 AC: 12143 AN: 41448

American (AMR) AF: 0.541 AC: 8273 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2204 AN: 3466

East Asian (EAS) AF: 0.627 AC: 3226 AN: 5144

South Asian (SAS) AF: 0.625 AC: 3004 AN: 4808

European-Finnish (FIN) AF: 0.715 AC: 7563 AN: 10582

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44932 AN: 67946

Other (OTH) AF: 0.531 AC: 1121 AN: 2112

Alfa AF: 0.633 Hom.: 15806

Bravo AF: 0.522

Asia WGS AF: 0.567 AC: 1975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.36
DANN	Benign	0.86
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs4979321; hg19: chr9-116769515; COSMIC: COSV55918570;