rs1348325

Variant names:

• chr17-8122394-A-G
• rs1348325
• NM_001165967.2:c.175T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-8122394-A-G
• chr17-8122394-A-C

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.175T>C​(p.Leu59Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,596,142 control chromosomes in the GnomAD database, including 13,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (3220 hom., cov: 31)
  • Exomes 𝑓: 0.11 (10072 hom.)
• Consequence: HES7 NM_001165967.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.78
• 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=-0.71).
• BP6: Variant 17-8122394-A-G is Benign according to our data. Variant chr17-8122394-A-G is described in ClinVar as Benign. ClinVar VariationId is 262088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.78 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 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.175T>C	p.Leu59Leu	synonymous	Exon 3 of 4	NP_001159439.1	Q9BYE0-2
	HES7	NM_032580.4		c.175T>C	p.Leu59Leu	synonymous	Exon 3 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.175T>C	p.Leu59Leu	synonymous	Exon 3 of 4	ENSP00000446205.2	Q9BYE0-2
	HES7	ENST00000317814.8	TSL:1	c.175T>C	p.Leu59Leu	synonymous	Exon 3 of 4	ENSP00000314774.4	Q9BYE0-1
	HES7	ENST00000577735.1	TSL:3	c.151T>C	p.Leu51Leu	synonymous	Exon 4 of 5	ENSP00000462491.1	J3KSH6

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25848 AN: 151548 Hom.: 3196 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.122 AC: 26518 AN: 217058 AF XY: 0.123

Gnomad AFR exome AF: 0.339

Gnomad AMR exome AF: 0.0871

Gnomad ASJ exome AF: 0.176

Gnomad EAS exome AF: 0.107

Gnomad FIN exome AF: 0.0812

Gnomad NFE exome AF: 0.0949

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.108 AC: 156224 AN: 1444474 Hom.: 10072 Cov.: 35 AF XY: 0.110 AC XY: 78923 AN XY: 716796

African (AFR) AF: 0.354 AC: 11692 AN: 33040

American (AMR) AF: 0.0925 AC: 3920 AN: 42398

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 4381 AN: 25686

East Asian (EAS) AF: 0.103 AC: 4022 AN: 38986

South Asian (SAS) AF: 0.179 AC: 14862 AN: 83228

European-Finnish (FIN) AF: 0.0857 AC: 4449 AN: 51916

Middle Eastern (MID) AF: 0.169 AC: 971 AN: 5740

European-Non Finnish (NFE) AF: 0.0946 AC: 104454 AN: 1103778

Other (OTH) AF: 0.125 AC: 7473 AN: 59702

GnomAD4 genome AF: 0.171 AC: 25916 AN: 151668 Hom.: 3220 Cov.: 31 AF XY: 0.170 AC XY: 12619 AN XY: 74148

African (AFR) AF: 0.346 AC: 14290 AN: 41276

American (AMR) AF: 0.127 AC: 1943 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3468

East Asian (EAS) AF: 0.104 AC: 534 AN: 5116

South Asian (SAS) AF: 0.178 AC: 855 AN: 4794

European-Finnish (FIN) AF: 0.0781 AC: 822 AN: 10530

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.0936 AC: 6354 AN: 67910

Other (OTH) AF: 0.160 AC: 336 AN: 2104

Alfa AF: 0.120 Hom.: 2066

Bravo AF: 0.181

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		1.8
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: rs1348325; hg19: chr17-8025712; COSMIC: COSV58554961; COSMIC: COSV58554961;