10-26445658-C-T

Variant names:

• chr10-26445658-C-T
• rs2992257
• NM_019043.4:c.-1+6805C>T

Variant summary

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

The NM_019043.4(APBB1IP):​c.-1+6805C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,206 control chromosomes in the GnomAD database, including 4,310 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 0.21 (4310 hom., cov: 33)
• Consequence: APBB1IP NM_019043.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB1IP	NM_019043.4	c.-1+6805C>T		intron_variant	Intron 2 of 14	ENST00000376236.9	NP_061916.3
APBB1IP	XM_011519514.3	c.-1+6805C>T		intron_variant	Intron 2 of 13		XP_011517816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB1IP	ENST00000376236.9	c.-1+6805C>T		intron_variant	Intron 2 of 14	5	NM_019043.4	ENSP00000365411.4
APBB1IP	ENST00000356785.4	c.-1+6805C>T		intron_variant	Intron 2 of 4	1		ENSP00000349237.4
APBB1IP	ENST00000718302.1	c.-1+6805C>T		intron_variant	Intron 2 of 14			ENSP00000520735.1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31998 AN: 152088 Hom.: 4305 Cov.: 33

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.196

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 32016 AN: 152206 Hom.: 4310 Cov.: 33 AF XY: 0.216 AC XY: 16039 AN XY: 74408

African (AFR) AF: 0.0517 AC: 2149 AN: 41552

American (AMR) AF: 0.149 AC: 2275 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3472

East Asian (EAS) AF: 0.492 AC: 2549 AN: 5180

South Asian (SAS) AF: 0.309 AC: 1490 AN: 4818

European-Finnish (FIN) AF: 0.336 AC: 3551 AN: 10576

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18519 AN: 67992

Other (OTH) AF: 0.192 AC: 406 AN: 2114

Alfa AF: 0.242 Hom.: 8862

Bravo AF: 0.189

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.76
PhyloP100		-0.20
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: rs2992257; hg19: chr10-26734587;