rs71660056

Variant names:

• chr6-152121768-CTT-C
• rs71660056
• ENST00000367251.7:c.*871_*872delAA

Your query was ambiguous. Multiple possible variants found:

• chr6-152121768-CTT-C
• chr6-152121768-CTT-CT
• chr6-152121768-CTT-CTTT
• chr6-152121768-CTT-CTTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000367251.7(SYNE1):​c.*871_*872delAA variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 150,818 control chromosomes in the GnomAD database, including 1,230 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1228 hom., cov: 0)
  • Exomes 𝑓: 0.11 (2 hom.)
• Consequence: SYNE1 ENST00000367251.7 splice_region
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.36
• Publications: 3 publications found

Genes affected

SYNE1 (HGNC:17089): (spectrin repeat containing nuclear envelope protein 1) This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia 8, also referred to as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ESR1 (HGNC:3467): (estrogen receptor 1) This gene encodes an estrogen receptor and ligand-activated transcription factor. The canonical protein contains an N-terminal ligand-independent transactivation domain, a central DNA binding domain, a hinge domain, and a C-terminal ligand-dependent transactivation domain. The protein localizes to the nucleus where it may form either a homodimer or a heterodimer with estrogen receptor 2. The protein encoded by this gene regulates the transcription of many estrogen-inducible genes that play a role in growth, metabolism, sexual development, gestation, and other reproductive functions and is expressed in many non-reproductive tissues. The receptor encoded by this gene plays a key role in breast cancer, endometrial cancer, and osteoporosis. This gene is reported to have dozens of transcript variants due to the use of alternate promoters and alternative splicing, however, the full-length nature of many of these variants remain uncertain. [provided by RefSeq, Jul 2020]

ESR1 Gene-Disease associations (from GenCC):

• estrogen resistance syndrome

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-152121768-CTT-C is Benign according to our data. Variant chr6-152121768-CTT-C is described in ClinVar as Benign. ClinVar VariationId is 355795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367251.7. 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
	SYNE1	NM_182961.4	MANE Select	c.*666_*667delAA		3_prime_UTR	Exon 146 of 146	NP_892006.3	Q8NF91-1
	SYNE1	NM_001347702.2	MANE Plus Clinical	c.*666_*667delAA		3_prime_UTR	Exon 18 of 18	NP_001334631.1	F8WAI0
	SYNE1	NM_033071.5		c.*666_*667delAA		3_prime_UTR	Exon 146 of 146	NP_149062.2	Q8NF91-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE1	ENST00000367251.7	TSL:1	c.*871_*872delAA		splice_region	Exon 31 of 31	ENSP00000356220.3	H0Y325
	SYNE1	ENST00000367255.10	TSL:1 MANE Select	c.*666_*667delAA		3_prime_UTR	Exon 146 of 146	ENSP00000356224.5	Q8NF91-1
	SYNE1	ENST00000354674.5	TSL:5 MANE Plus Clinical	c.*666_*667delAA		3_prime_UTR	Exon 18 of 18	ENSP00000346701.4	F8WAI0

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17612 AN: 150178 Hom.: 1229 Cov.: 0

Gnomad AFR AF: 0.0683

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.109 AC: 58 AN: 534 Hom.: 2 AF XY: 0.127 AC XY: 41 AN XY: 324

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.100 AC: 42 AN: 418

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.150 AC: 15 AN: 100

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.117 AC: 17622 AN: 150284 Hom.: 1228 Cov.: 0 AF XY: 0.121 AC XY: 8922 AN XY: 73442

African (AFR) AF: 0.0684 AC: 2806 AN: 41028

American (AMR) AF: 0.172 AC: 2586 AN: 15072

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 320 AN: 3436

East Asian (EAS) AF: 0.307 AC: 1573 AN: 5126

South Asian (SAS) AF: 0.224 AC: 1064 AN: 4750

European-Finnish (FIN) AF: 0.113 AC: 1150 AN: 10176

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7676 AN: 67414

Other (OTH) AF: 0.150 AC: 311 AN: 2080

Alfa AF: 0.0540 Hom.: 548

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cerebellar ataxia (1)
-	-	1	Emery-Dreifuss muscular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
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: rs71660056; hg19: chr6-152442903; COSMIC: COSV54897136; COSMIC: COSV54897136;