rs56066045

Variant names:

• chr17-8121862-T-C
• rs56066045
• NM_001165967.2:c.402A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-8121862-T-C
• chr17-8121862-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001165967.2(HES7):​c.402A>G​(p.Lys134Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,564,774 control chromosomes in the GnomAD database, including 9,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1953 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7872 hom.)
• Consequence: HES7 NM_001165967.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.763
• Publications: 11 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 17-8121862-T-C is Benign according to our data. Variant chr17-8121862-T-C is described in ClinVar as Benign. ClinVar VariationId is 262089.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.763 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 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.402A>G	p.Lys134Lys	synonymous	Exon 4 of 4	NP_001159439.1	Q9BYE0-2
	HES7	NM_032580.4		c.387A>G	p.Lys129Lys	synonymous	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.402A>G	p.Lys134Lys	synonymous	Exon 4 of 4	ENSP00000446205.2	Q9BYE0-2
	HES7	ENST00000317814.8	TSL:1	c.387A>G	p.Lys129Lys	synonymous	Exon 4 of 4	ENSP00000314774.4	Q9BYE0-1
	HES7	ENST00000577735.1	TSL:3	c.378A>G	p.Lys126Lys	synonymous	Exon 5 of 5	ENSP00000462491.1	J3KSH6

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21490 AN: 150386 Hom.: 1949 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0932

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0797

Gnomad MID AF: 0.198

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.141

GnomAD2 exomes AF: 0.107 AC: 19914 AN: 185598 AF XY: 0.108

Gnomad AFR exome AF: 0.239

Gnomad AMR exome AF: 0.0814

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.0961

Gnomad FIN exome AF: 0.0827

Gnomad NFE exome AF: 0.0970

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.102 AC: 143561 AN: 1414282 Hom.: 7872 Cov.: 32 AF XY: 0.102 AC XY: 72025 AN XY: 703424

African (AFR) AF: 0.249 AC: 7358 AN: 29500

American (AMR) AF: 0.0866 AC: 3620 AN: 41798

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 4176 AN: 24738

East Asian (EAS) AF: 0.0972 AC: 3512 AN: 36140

South Asian (SAS) AF: 0.122 AC: 10144 AN: 83252

European-Finnish (FIN) AF: 0.0872 AC: 3207 AN: 36766

Middle Eastern (MID) AF: 0.168 AC: 770 AN: 4586

European-Non Finnish (NFE) AF: 0.0947 AC: 104082 AN: 1098882

Other (OTH) AF: 0.114 AC: 6692 AN: 58620

GnomAD4 genome AF: 0.143 AC: 21507 AN: 150492 Hom.: 1953 Cov.: 32 AF XY: 0.142 AC XY: 10460 AN XY: 73532

African (AFR) AF: 0.253 AC: 10377 AN: 40992

American (AMR) AF: 0.119 AC: 1802 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 577 AN: 3444

East Asian (EAS) AF: 0.0934 AC: 476 AN: 5094

South Asian (SAS) AF: 0.127 AC: 597 AN: 4704

European-Finnish (FIN) AF: 0.0797 AC: 832 AN: 10434

Middle Eastern (MID) AF: 0.203 AC: 58 AN: 286

European-Non Finnish (NFE) AF: 0.0942 AC: 6348 AN: 67366

Other (OTH) AF: 0.140 AC: 293 AN: 2096

Alfa AF: 0.115 Hom.: 224

Bravo AF: 0.150

Asia WGS AF: 0.121 AC: 419 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56066045; hg19: chr17-8025180; COSMIC: COSV58554884; COSMIC: COSV58554884;