rs17778240

Variant names:

• chr22-35077185-A-T
• rs17778240
• NM_001303508.2:c.230-5333A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

LINC01399 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303508.2. 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
	ISX	NM_001303508.2	MANE Select	c.230-5333A>T		intron	N/A	NP_001290437.1
	ISX	NM_001438732.1		c.230-5333A>T		intron	N/A	NP_001425661.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISX	ENST00000404699.7	TSL:1 MANE Select	c.230-5333A>T		intron	N/A	ENSP00000386037.1
	ISX	ENST00000308700.6	TSL:1	c.230-5333A>T		intron	N/A	ENSP00000311492.6
	LINC01399	ENST00000798716.1		n.353-928T>A		intron	N/A

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

African (AFR) AF: 0.295 AC: 12260 AN: 41496

American (AMR) AF: 0.452 AC: 6910 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1633 AN: 3470

East Asian (EAS) AF: 0.151 AC: 779 AN: 5174

South Asian (SAS) AF: 0.267 AC: 1291 AN: 4830

European-Finnish (FIN) AF: 0.427 AC: 4525 AN: 10586

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34215 AN: 67950

Other (OTH) AF: 0.428 AC: 904 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.76
PhyloP100		0.30
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: rs17778240; hg19: chr22-35473178;