rs8076629

Variant names:

• chr17-8121490-C-A
• rs8076629
• NM_001165967.2:c.*81G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-8121490-C-A
• chr17-8121490-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001165967.2(HES7):​c.*81G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,215,036 control chromosomes in the GnomAD database, including 6,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1368 hom., cov: 32)
  • Exomes 𝑓: 0.098 (5402 hom.)
• Consequence: HES7 NM_001165967.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.635
• Publications: 5 publications found

Genes affected

HES7 (HGNC:15977): (hes family bHLH transcription factor 7) This gene encodes a member of the hairy and enhancer of split family of bHLH transcription factors. The mouse ortholog of this gene is regulated by Notch signaling. The protein functions as a transcriptional repressor, and is implicated in correct patterning of the axial skeleton. A mutation in this gene has been shown to result in spondylocostal dysostosis. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

HES7 Gene-Disease associations (from GenCC):

• spondylocostal dysostosis 4, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal recessive spondylocostal dysostosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 17-8121490-C-A is Benign according to our data. Variant chr17-8121490-C-A is described in ClinVar as Benign. ClinVar VariationId is 1291988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165967.2. 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
	HES7	NM_001165967.2	MANE Select	c.*81G>T		3_prime_UTR	Exon 4 of 4	NP_001159439.1	Q9BYE0-2
	HES7	NM_032580.4		c.*81G>T		3_prime_UTR	Exon 4 of 4	NP_115969.2	Q9BYE0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HES7	ENST00000541682.7	TSL:1 MANE Select	c.*81G>T		3_prime_UTR	Exon 4 of 4	ENSP00000446205.2	Q9BYE0-2
	HES7	ENST00000317814.8	TSL:1	c.*81G>T		downstream_gene	N/A	ENSP00000314774.4	Q9BYE0-1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18893 AN: 152128 Hom.: 1367 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0920

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.0982 AC: 104390 AN: 1062794 Hom.: 5402 Cov.: 18 AF XY: 0.0987 AC XY: 49861 AN XY: 504992

African (AFR) AF: 0.194 AC: 4286 AN: 22078

American (AMR) AF: 0.0995 AC: 846 AN: 8500

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 2468 AN: 14868

East Asian (EAS) AF: 0.0954 AC: 2517 AN: 26378

South Asian (SAS) AF: 0.115 AC: 2854 AN: 24750

European-Finnish (FIN) AF: 0.0880 AC: 2039 AN: 23162

Middle Eastern (MID) AF: 0.162 AC: 486 AN: 3004

European-Non Finnish (NFE) AF: 0.0938 AC: 84072 AN: 895940

Other (OTH) AF: 0.109 AC: 4822 AN: 44114

GnomAD4 genome AF: 0.124 AC: 18902 AN: 152242 Hom.: 1368 Cov.: 32 AF XY: 0.125 AC XY: 9268 AN XY: 74434

African (AFR) AF: 0.191 AC: 7952 AN: 41536

American (AMR) AF: 0.109 AC: 1664 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3472

East Asian (EAS) AF: 0.0923 AC: 477 AN: 5170

South Asian (SAS) AF: 0.123 AC: 596 AN: 4830

European-Finnish (FIN) AF: 0.0785 AC: 833 AN: 10618

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0931 AC: 6330 AN: 67988

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.107 Hom.: 1498

Bravo AF: 0.130

Asia WGS AF: 0.117 AC: 406 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_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.71
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs8076629; hg19: chr17-8024808; COSMIC: COSV58554725; COSMIC: COSV58554725;