rs2413338

Variant names:

• chr22-35267530-C-T
• rs2413338
• NM_001003681.3:c.1215+1927C>T

Variant summary

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

The NM_001003681.3(HMGXB4):​c.1215+1927C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,936 control chromosomes in the GnomAD database, including 20,839 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 0.48 (20839 hom., cov: 31)
• Consequence: HMGXB4 NM_001003681.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 14 publications found

Genes affected

HMGXB4 (HGNC:5003): (HMG-box containing 4) High mobility group (HMG) proteins are nonhistone chromosomal proteins. See HMG2 (MIM 163906) for additional information on HMG proteins.[supplied by OMIM, Nov 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003681.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB4	NM_001003681.3	MANE Select	c.1215+1927C>T		intron	N/A	NP_001003681.1
	HMGXB4	NM_001362972.2		c.888+1927C>T		intron	N/A	NP_001349901.1
	HMGXB4	NR_027780.2		n.1463+1927C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB4	ENST00000216106.6	TSL:5 MANE Select	c.1215+1927C>T		intron	N/A	ENSP00000216106.5
	HMGXB4	ENST00000418170.5	TSL:1	n.*1051+1927C>T		intron	N/A	ENSP00000395532.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72261 AN: 151818 Hom.: 20855 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.475 AC: 72236 AN: 151936 Hom.: 20839 Cov.: 31 AF XY: 0.476 AC XY: 35352 AN XY: 74248

African (AFR) AF: 0.126 AC: 5212 AN: 41464

American (AMR) AF: 0.532 AC: 8111 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2295 AN: 3464

East Asian (EAS) AF: 0.539 AC: 2782 AN: 5158

South Asian (SAS) AF: 0.565 AC: 2719 AN: 4812

European-Finnish (FIN) AF: 0.610 AC: 6428 AN: 10534

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42822 AN: 67940

Other (OTH) AF: 0.531 AC: 1118 AN: 2104

Alfa AF: 0.578 Hom.: 66659

Bravo AF: 0.457

Asia WGS AF: 0.529 AC: 1839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.62
PhyloP100		-0.54
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: rs2413338; hg19: chr22-35663523;