rs7170852

Variant names:

• chr15-28182840-T-A
• rs7170852
• NM_004667.6:c.8826-328A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-28182840-T-A
• chr15-28182840-T-C
• chr15-28182840-T-G

Variant summary

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

The NM_004667.6(HERC2):​c.8826-328A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,144 control chromosomes in the GnomAD database, including 36,193 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 0.64 (36193 hom., cov: 32)
• Consequence: HERC2 NM_004667.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 16 publications found

Genes affected

HERC2 (HGNC:4868): (HECT and RLD domain containing E3 ubiquitin protein ligase 2) This gene belongs to the HERC gene family that encodes a group of unusually large proteins, which contain multiple structural domains. All members have at least 1 copy of an N-terminal region showing homology to the cell cycle regulator RCC1 and a C-terminal HECT (homologous to E6-AP C terminus) domain found in a number of E3 ubiquitin protein ligases. Genetic variations in this gene are associated with skin/hair/eye pigmentation variability. Multiple pseudogenes of this gene are located on chromosomes 15 and 16. [provided by RefSeq, Mar 2012]

HERC2 Gene-Disease associations (from GenCC):

• developmental delay with autism spectrum disorder and gait instability

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004667.6. 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
	HERC2	NM_004667.6	MANE Select	c.8826-328A>T		intron	N/A	NP_004658.3	O95714

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERC2	ENST00000261609.13	TSL:1 MANE Select	c.8826-328A>T		intron	N/A	ENSP00000261609.8	O95714
	HERC2	ENST00000650509.1		n.537-328A>T		intron	N/A	ENSP00000496936.1	A0A3B3IRP6

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97221 AN: 152026 Hom.: 36199 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.607

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.639 AC: 97222 AN: 152144 Hom.: 36193 Cov.: 32 AF XY: 0.634 AC XY: 47162 AN XY: 74394

African (AFR) AF: 0.294 AC: 12187 AN: 41490

American (AMR) AF: 0.601 AC: 9177 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2562 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1373 AN: 5160

South Asian (SAS) AF: 0.425 AC: 2050 AN: 4822

European-Finnish (FIN) AF: 0.953 AC: 10126 AN: 10628

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.849 AC: 57722 AN: 67986

Other (OTH) AF: 0.604 AC: 1273 AN: 2108

Alfa AF: 0.749 Hom.: 5776

Bravo AF: 0.600

Asia WGS AF: 0.378 AC: 1316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.055
DANN	Benign	0.38
PhyloP100		-1.5
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: rs7170852; hg19: chr15-28427986;