chr22-35077185-A-T

Position:

• chr22-35077185-A-T

Variant summary

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

The NM_001303508.2(ISX):​c.230-5333A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,112 control chromosomes in the GnomAD database, including 13,985 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 0.42 (13985 hom., cov: 32)
• Consequence: ISX NM_001303508.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296

Genes affected

ISX (HGNC:28084): (intestine specific homeobox) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the RAXLX homeobox gene family. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISX	NM_001303508.2	c.230-5333A>T		intron_variant		ENST00000404699.7	NP_001290437.1
ISX	XM_047441598.1	c.230-5333A>T		intron_variant			XP_047297554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISX	ENST00000404699.7	c.230-5333A>T		intron_variant		1	NM_001303508.2	ENSP00000386037.1
ISX	ENST00000308700.6	c.230-5333A>T		intron_variant		1		ENSP00000311492.6

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63146 AN: 151994 Hom.: 13977 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.415 AC: 63182 AN: 152112 Hom.: 13985 Cov.: 32 AF XY: 0.408 AC XY: 30325 AN XY: 74364

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.428

Alfa AF: 0.461 Hom.: 2083

Bravo AF: 0.415

Asia WGS AF: 0.199 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.76

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: rs17778240; hg19: chr22-35473178;