rs1775246

Variant names:

• chr10-26492459-G-A
• rs1775246
• NM_019043.4:c.72+61G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019043.4(APBB1IP):​c.72+61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 1,480,308 control chromosomes in the GnomAD database, including 439,933 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.80 (49552 hom., cov: 32)
  • Exomes 𝑓: 0.76 (390381 hom.)
• Consequence: APBB1IP NM_019043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 8 publications found

Genes affected

APBB1IP (HGNC:17379): (amyloid beta precursor protein binding family B member 1 interacting protein) Predicted to be involved in signal transduction. Predicted to act upstream of or within T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell and positive regulation of cell adhesion. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB1IP	NM_019043.4	c.72+61G>A		intron_variant	Intron 3 of 14	ENST00000376236.9	NP_061916.3
APBB1IP	XM_011519514.3	c.72+61G>A		intron_variant	Intron 3 of 13		XP_011517816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB1IP	ENST00000376236.9	c.72+61G>A		intron_variant	Intron 3 of 14	5	NM_019043.4	ENSP00000365411.4
APBB1IP	ENST00000356785.4	c.72+61G>A		intron_variant	Intron 3 of 4	1		ENSP00000349237.4
APBB1IP	ENST00000718302.1	c.72+61G>A		intron_variant	Intron 3 of 14			ENSP00000520735.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122209 AN: 152090 Hom.: 49490 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.784

GnomAD4 exome AF: 0.765 AC: 1015706 AN: 1328100 Hom.: 390381 AF XY: 0.766 AC XY: 511476 AN XY: 667890

African (AFR) AF: 0.888 AC: 26945 AN: 30332

American (AMR) AF: 0.847 AC: 36554 AN: 43154

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 20280 AN: 25140

East Asian (EAS) AF: 0.911 AC: 35463 AN: 38940

South Asian (SAS) AF: 0.821 AC: 67902 AN: 82690

European-Finnish (FIN) AF: 0.823 AC: 43538 AN: 52902

Middle Eastern (MID) AF: 0.785 AC: 4278 AN: 5448

European-Non Finnish (NFE) AF: 0.742 AC: 737596 AN: 993796

Other (OTH) AF: 0.775 AC: 43150 AN: 55698

GnomAD4 genome AF: 0.804 AC: 122328 AN: 152208 Hom.: 49552 Cov.: 32 AF XY: 0.808 AC XY: 60148 AN XY: 74400

African (AFR) AF: 0.886 AC: 36798 AN: 41530

American (AMR) AF: 0.785 AC: 12015 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2831 AN: 3472

East Asian (EAS) AF: 0.888 AC: 4592 AN: 5170

South Asian (SAS) AF: 0.827 AC: 3988 AN: 4824

European-Finnish (FIN) AF: 0.835 AC: 8857 AN: 10604

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50638 AN: 67982

Other (OTH) AF: 0.787 AC: 1663 AN: 2114

Alfa AF: 0.767 Hom.: 15354

Bravo AF: 0.806

Asia WGS AF: 0.853 AC: 2964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.67
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1775246; hg19: chr10-26781388;