7-64068891-C-T

Variant names:

• chr7-64068891-C-T
• rs10237332
• NM_001159522.3:c.4C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001159522.3(ZNF727):​c.4C>T​(p.Arg2*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,589,956 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (51 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (47 hom.)
• Consequence: ZNF727 NM_001159522.3 stop_gained, splice_region
• Scores: Splicing: ADA: 0.00005457
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36
• Publications: 3 publications found

Genes affected

ZNF727 (HGNC:22785): (zinc finger protein 727) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-64068891-C-T is Benign according to our data. Variant chr7-64068891-C-T is described in ClinVar as Benign. ClinVar VariationId is 787051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0136 (2072/152096) while in subpopulation AFR AF = 0.047 (1951/41498). AF 95% confidence interval is 0.0453. There are 51 homozygotes in GnomAd4. There are 991 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 51 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159522.3. 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
	ZNF727	NM_001159522.3	MANE Select	c.4C>T	p.Arg2*	stop_gained splice_region	Exon 2 of 4	NP_001152994.1	A8MUV8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF727	ENST00000456806.3	TSL:4 MANE Select	c.4C>T	p.Arg2*	stop_gained splice_region	Exon 2 of 4	ENSP00000485448.1	A8MUV8
	ZNF727	ENST00000889951.1		c.4C>T	p.Arg2*	stop_gained splice_region	Exon 2 of 4	ENSP00000560010.1
	ZNF727	ENST00000889950.1		c.4C>T	p.Arg2*	stop_gained splice_region	Exon 2 of 3	ENSP00000560009.1

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2065 AN: 151978 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00525

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000773

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00720

GnomAD2 exomes AF: 0.00354 AC: 769 AN: 217012 AF XY: 0.00283

Gnomad AFR exome AF: 0.0482

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000191

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000295

Gnomad OTH exome AF: 0.00274

GnomAD4 exome AF: 0.00162 AC: 2330 AN: 1437860 Hom.: 47 Cov.: 31 AF XY: 0.00139 AC XY: 995 AN XY: 713536

African (AFR) AF: 0.0485 AC: 1582 AN: 32592

American (AMR) AF: 0.00355 AC: 145 AN: 40900

Ashkenazi Jewish (ASJ) AF: 0.0000388 AC: 1 AN: 25760

East Asian (EAS) AF: 0.00224 AC: 86 AN: 38310

South Asian (SAS) AF: 0.0000597 AC: 5 AN: 83776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51912

Middle Eastern (MID) AF: 0.00279 AC: 16 AN: 5732

European-Non Finnish (NFE) AF: 0.000261 AC: 287 AN: 1099392

Other (OTH) AF: 0.00350 AC: 208 AN: 59486

GnomAD4 genome AF: 0.0136 AC: 2072 AN: 152096 Hom.: 51 Cov.: 32 AF XY: 0.0133 AC XY: 991 AN XY: 74364

African (AFR) AF: 0.0470 AC: 1951 AN: 41498

American (AMR) AF: 0.00524 AC: 80 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000775 AC: 4 AN: 5160

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 67990

Other (OTH) AF: 0.00712 AC: 15 AN: 2106

Alfa AF: 0.00703 Hom.: 24

Bravo AF: 0.0159

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0376 AC: 52

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00390 AC: 470

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	33
DANN	Benign	0.94
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.010	N
PhyloP100		-1.4
Vest4		0.030
GERP RS		-0.30

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000055
dbscSNV1_RF	Benign	0.092
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: rs10237332; hg19: chr7-63529269;