rs1799755

Variant names:

• chr11-6395774-CTAG-C
• rs1799755
• NM_001164.5:c.1965+9_1965+11delCTA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001164.5(APBB1):​c.1965+9_1965+11delCTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,613,122 control chromosomes in the GnomAD database, including 19,806 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2133 hom., cov: 29)
  • Exomes 𝑓: 0.15 (17673 hom.)
• Consequence: APBB1 NM_001164.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 2 publications found

Genes affected

APBB1 (HGNC:581): (amyloid beta precursor protein binding family B member 1) The protein encoded by this gene is a member of the Fe65 protein family. It is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164.5. 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
	APBB1	NM_001164.5	MANE Select	c.1965+9_1965+11delCTA		intron	N/A	NP_001155.1	O00213-1
	APBB1	NM_145689.3		c.1959+9_1959+11delCTA		intron	N/A	NP_663722.1	O00213-2
	APBB1	NM_001257319.3		c.1305+9_1305+11delCTA		intron	N/A	NP_001244248.1	O00213-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBB1	ENST00000609360.6	TSL:5 MANE Select	c.1965+9_1965+11delCTA		intron	N/A	ENSP00000477213.1	O00213-1
	APBB1	ENST00000311051.7	TSL:1	c.1959+9_1959+11delCTA		intron	N/A	ENSP00000311912.3	O00213-2
	APBB1	ENST00000905160.1		c.2016+9_2016+11delCTA		intron	N/A	ENSP00000575219.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24403 AN: 151962 Hom.: 2124 Cov.: 29

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.163

GnomAD2 exomes AF: 0.150 AC: 37393 AN: 249784 AF XY: 0.154

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.00691

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.149 AC: 217161 AN: 1461042 Hom.: 17673 AF XY: 0.152 AC XY: 110429 AN XY: 726802

African (AFR) AF: 0.229 AC: 7664 AN: 33470

American (AMR) AF: 0.145 AC: 6488 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 3194 AN: 26044

East Asian (EAS) AF: 0.00443 AC: 176 AN: 39692

South Asian (SAS) AF: 0.262 AC: 22622 AN: 86190

European-Finnish (FIN) AF: 0.110 AC: 5839 AN: 53324

Middle Eastern (MID) AF: 0.171 AC: 988 AN: 5764

European-Non Finnish (NFE) AF: 0.145 AC: 161303 AN: 1111542

Other (OTH) AF: 0.147 AC: 8887 AN: 60354

GnomAD4 genome AF: 0.161 AC: 24438 AN: 152080 Hom.: 2133 Cov.: 29 AF XY: 0.161 AC XY: 11963 AN XY: 74346

African (AFR) AF: 0.221 AC: 9172 AN: 41444

American (AMR) AF: 0.148 AC: 2263 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3470

East Asian (EAS) AF: 0.00560 AC: 29 AN: 5176

South Asian (SAS) AF: 0.250 AC: 1207 AN: 4822

European-Finnish (FIN) AF: 0.103 AC: 1089 AN: 10602

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.144 AC: 9802 AN: 67960

Other (OTH) AF: 0.163 AC: 344 AN: 2114

Alfa AF: 0.150 Hom.: 310

Bravo AF: 0.165

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.25
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: rs1799755; hg19: chr11-6417004;