chr1-246864477-T-C

Variant names:

• chr1-246864477-T-C
• rs1691251
• NM_001323342.2:c.3348-361A>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.3348-361A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,066 control chromosomes in the GnomAD database, including 35,159 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 0.66 (35159 hom., cov: 31)
• Consequence: AHCTF1 NM_001323342.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHCTF1	NM_001323342.2	MANE Select	c.3348-361A>G		intron	N/A	NP_001310271.1	Q8WYP5-1
	AHCTF1	NM_001410950.1		c.3453-361A>G		intron	N/A	NP_001397879.1	Q8WYP5-2
	AHCTF1	NM_015446.5		c.3375-361A>G		intron	N/A	NP_056261.4	Q8WYP5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHCTF1	ENST00000648844.2	MANE Select	c.3348-361A>G		intron	N/A	ENSP00000497061.2	Q8WYP5-1
	AHCTF1	ENST00000326225.3	TSL:1	c.3375-361A>G		intron	N/A	ENSP00000355465.1	Q8WYP5-3
	AHCTF1	ENST00000470300.5	TSL:1	n.1963-361A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.658 AC: 100001 AN: 151948 Hom.: 35086 Cov.: 31

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.659 AC: 100141 AN: 152066 Hom.: 35159 Cov.: 31 AF XY: 0.663 AC XY: 49307 AN XY: 74316

African (AFR) AF: 0.909 AC: 37751 AN: 41534

American (AMR) AF: 0.682 AC: 10404 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1525 AN: 3472

East Asian (EAS) AF: 0.595 AC: 3078 AN: 5172

South Asian (SAS) AF: 0.515 AC: 2480 AN: 4818

European-Finnish (FIN) AF: 0.686 AC: 7233 AN: 10542

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35513 AN: 67944

Other (OTH) AF: 0.640 AC: 1351 AN: 2112

Alfa AF: 0.569 Hom.: 68156

Bravo AF: 0.677

Asia WGS AF: 0.557 AC: 1935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.3
DANN	Benign	0.44
PhyloP100		-0.36
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: rs1691251; hg19: chr1-247027779;