1-246917020-T-C

Variant names:

• chr1-246917020-T-C
• rs1892116
• NM_001323342.2:c.122-625A>G

Variant summary

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

The NM_001323342.2(AHCTF1):​c.122-625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,124 control chromosomes in the GnomAD database, including 4,582 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 0.24 (4582 hom., cov: 32)
• Consequence: AHCTF1 NM_001323342.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 3 publications found

Genes affected

AHCTF1 (HGNC:24618): (AT-hook containing transcription factor 1) Predicted to enable DNA binding activity. Involved in nuclear pore complex assembly and regulation of cytokinesis. Located in nuclear membrane. Colocalizes with chromatin; kinetochore; and nuclear pore outer ring. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323342.2. 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
	AHCTF1	NM_001323342.2	MANE Select	c.122-625A>G		intron	N/A	NP_001310271.1
	AHCTF1	NM_001410950.1		c.227-625A>G		intron	N/A	NP_001397879.1
	AHCTF1	NM_015446.5		c.149-625A>G		intron	N/A	NP_056261.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHCTF1	ENST00000648844.2	MANE Select	c.122-625A>G		intron	N/A	ENSP00000497061.2
	AHCTF1	ENST00000326225.3	TSL:1	c.149-625A>G		intron	N/A	ENSP00000355465.1
	AHCTF1	ENST00000366508.5	TSL:5	c.227-625A>G		intron	N/A	ENSP00000355464.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36630 AN: 152006 Hom.: 4580 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.241 AC: 36638 AN: 152124 Hom.: 4582 Cov.: 32 AF XY: 0.247 AC XY: 18338 AN XY: 74342

African (AFR) AF: 0.231 AC: 9588 AN: 41510

American (AMR) AF: 0.264 AC: 4037 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 654 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1622 AN: 5178

South Asian (SAS) AF: 0.201 AC: 971 AN: 4828

European-Finnish (FIN) AF: 0.336 AC: 3551 AN: 10556

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15386 AN: 67986

Other (OTH) AF: 0.207 AC: 437 AN: 2112

Alfa AF: 0.238 Hom.: 1540

Bravo AF: 0.239

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.7
DANN	Benign	0.59
PhyloP100		0.20
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: rs1892116; hg19: chr1-247080322;