rs11621145

Variant names:

• chr14-105706543-G-A
• rs11621145
• ENST00000641837.1:c.1000+687C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

IGH (HGNC:5477):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641837.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHA1	ENST00000641837.1		c.1000+687C>T		intron	N/A	ENSP00000493114.1	P01876-2

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

African (AFR) AF: 0.127 AC: 5237 AN: 41334

American (AMR) AF: 0.417 AC: 6327 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2479 AN: 3452

East Asian (EAS) AF: 0.647 AC: 3297 AN: 5094

South Asian (SAS) AF: 0.571 AC: 2718 AN: 4762

European-Finnish (FIN) AF: 0.617 AC: 6466 AN: 10474

Middle Eastern (MID) AF: 0.640 AC: 178 AN: 278

European-Non Finnish (NFE) AF: 0.686 AC: 46323 AN: 67478

Other (OTH) AF: 0.539 AC: 1123 AN: 2084

Alfa AF: 0.585 Hom.: 3584

Asia WGS AF: 0.580 AC: 2017 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.7
DANN	Benign	0.51
PhyloP100		-1.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11621145;

hg19: chr14-106172880;