rs1335540

Variant names:

• chr10-26438309-T-A
• rs1335540
• NM_019043.4:c.-349T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-26438309-T-A
• chr10-26438309-T-C
• chr10-26438309-T-G

Variant summary

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

The NM_019043.4(APBB1IP):​c.-349T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,988 control chromosomes in the GnomAD database, including 28,500 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 0.61 (28484 hom., cov: 30)
  • Exomes 𝑓: 0.71 (16 hom.)
• Consequence: APBB1IP NM_019043.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 13 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB1IP	NM_019043.4	c.-349T>A		upstream_gene_variant		ENST00000376236.9	NP_061916.3
APBB1IP	XM_011519514.3	c.-349T>A		upstream_gene_variant			XP_011517816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB1IP	ENST00000376236.9	c.-349T>A		upstream_gene_variant		5	NM_019043.4	ENSP00000365411.4
APBB1IP	ENST00000356785.4	c.-349T>A		upstream_gene_variant		1		ENSP00000349237.4
APBB1IP	ENST00000718302.1	c.-349T>A		upstream_gene_variant				ENSP00000520735.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92064 AN: 151808 Hom.: 28459 Cov.: 30

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.710 AC: 44 AN: 62 Hom.: 16 Cov.: 0 AF XY: 0.727 AC XY: 32 AN XY: 44

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 6 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.682 AC: 30 AN: 44

Other (OTH) AF: 0.833 AC: 5 AN: 6

GnomAD4 genome AF: 0.606 AC: 92130 AN: 151926 Hom.: 28484 Cov.: 30 AF XY: 0.617 AC XY: 45822 AN XY: 74220

African (AFR) AF: 0.518 AC: 21471 AN: 41438

American (AMR) AF: 0.615 AC: 9393 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1964 AN: 3470

East Asian (EAS) AF: 0.932 AC: 4783 AN: 5130

South Asian (SAS) AF: 0.803 AC: 3870 AN: 4820

European-Finnish (FIN) AF: 0.696 AC: 7353 AN: 10564

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41254 AN: 67920

Other (OTH) AF: 0.604 AC: 1274 AN: 2108

Alfa AF: 0.607 Hom.: 3486

Bravo AF: 0.595

Asia WGS AF: 0.829 AC: 2880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.20
DANN	Benign	0.68
PhyloP100		-2.2
PromoterAI		0.042	Neutral
Mutation Taster		=299/1	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: rs1335540; hg19: chr10-26727238;