chr11-61958127-A-ATCCTCC

Position:

• chr11-61958127-A-ATCCTCC

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP6_Moderate BS2_Supporting

The NM_004183.4(BEST1):​c.715-9_715-4dupTCCTCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000060 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00026 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BEST1 NM_004183.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.82

Genes affected

BEST1 (HGNC:12703): (bestrophin 1) This gene encodes a member of the bestrophin gene family. This small gene family is characterized by proteins with a highly conserved N-terminus with four to six transmembrane domains. Bestrophins may form chloride ion channels or may regulate voltage-gated L-type calcium-ion channels. Bestrophins are generally believed to form calcium-activated chloride-ion channels in epithelial cells but they have also been shown to be highly permeable to bicarbonate ion transport in retinal tissue. Mutations in this gene are responsible for juvenile-onset vitelliform macular dystrophy (VMD2), also known as Best macular dystrophy, in addition to adult-onset vitelliform macular dystrophy (AVMD) and other retinopathies. Alternative splicing results in multiple variants encoding distinct isoforms.[provided by RefSeq, Nov 2008]

LOC107984334 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• BP6: Variant 11-61958127-A-ATCCTCC is Benign according to our data. Variant chr11-61958127-A-ATCCTCC is described in ClinVar as [Likely_benign]. Clinvar id is 1123172.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 9 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BEST1	NM_004183.4	c.715-9_715-4dupTCCTCC		splice_region_variant, intron_variant		ENST00000378043.9	NP_004174.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BEST1	ENST00000378043.9	c.715-9_715-4dupTCCTCC		splice_region_variant, intron_variant		1	NM_004183.4	ENSP00000367282.4

Frequencies

GnomAD3 genomes AF: 0.0000596 AC: 9 AN: 151040 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000261 AC: 317 AN: 1215380 Hom.: 0 Cov.: 82 AF XY: 0.000253 AC XY: 153 AN XY: 603892

Gnomad4 AFR exome AF: 0.000398

Gnomad4 AMR exome AF: 0.000242

Gnomad4 ASJ exome AF: 0.0000965

Gnomad4 EAS exome AF: 0.000228

Gnomad4 SAS exome AF: 0.000276

Gnomad4 FIN exome AF: 0.00224

Gnomad4 NFE exome AF: 0.000168

Gnomad4 OTH exome AF: 0.000281

GnomAD4 genome AF: 0.0000595 AC: 9 AN: 151154 Hom.: 0 Cov.: 0 AF XY: 0.0000542 AC XY: 4 AN XY: 73828

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000296

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0917 Hom.: 4495

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1805182; hg19: chr11-61725599;