rs11621145

Positions:

• chr14-105706543-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000641837.1(IGHA1):​c.1000+687C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,036 control chromosomes in the GnomAD database, including 22,382 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 0.50 (22382 hom., cov: 32)
• Consequence: IGHA1 ENST00000641837.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997

Genes affected

IGHA1 (HGNC:5478): (immunoglobulin heavy constant alpha 1) Contributes to immunoglobulin receptor binding activity. Involved in antibacterial humoral response; glomerular filtration; and positive regulation of respiratory burst. Located in extracellular space. Part of monomeric IgA immunoglobulin complex and secretory dimeric IgA immunoglobulin complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGHA1	ENST00000641837.1	c.1000+687C>T		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 74825 AN: 150920 Hom.: 22389 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.657

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.495 AC: 74809 AN: 151036 Hom.: 22382 Cov.: 32 AF XY: 0.491 AC XY: 36217 AN XY: 73746

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.539

Alfa AF: 0.585 Hom.: 3584

Asia WGS AF: 0.580 AC: 2017 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.7
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11621145; hg19: chr14-106172880;