rs2413338

Positions:

• chr22-35267530-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGXB4	NM_001003681.3	c.1215+1927C>T		intron_variant		ENST00000216106.6	NP_001003681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGXB4	ENST00000216106.6	c.1215+1927C>T		intron_variant		5	NM_001003681.3	ENSP00000216106.5
HMGXB4	ENST00000418170.5	n.*1051+1927C>T		intron_variant		1		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

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.531

Alfa AF: 0.610 Hom.: 50952

Bravo AF: 0.457

Asia WGS AF: 0.529 AC: 1839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs2413338; hg19: chr22-35663523;