chr3-52210035-A-T

Variant names:

• chr3-52210035-A-T
• rs11712164
• NM_000688.6:c.1331-1248A>T

Variant summary

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

The NM_001304444.1(ALAS1):​c.1382-1248A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,106 control chromosomes in the GnomAD database, including 9,237 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 0.33 (9237 hom., cov: 32)
• Consequence: ALAS1 NM_001304444.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 16 publications found

Genes affected

ALAS1 (HGNC:396): (5'-aminolevulinate synthase 1) This gene encodes the mitochondrial enzyme which is catalyzes the rate-limiting step in heme (iron-protoporphyrin) biosynthesis. The enzyme encoded by this gene is the housekeeping enzyme; a separate gene encodes a form of the enzyme that is specific for erythroid tissue. The level of the mature encoded protein is regulated by heme: high levels of heme down-regulate the mature enzyme in mitochondria while low heme levels up-regulate. A pseudogene of this gene is located on chromosome 12. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304444.1. 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
	ALAS1	NM_000688.6	MANE Select	c.1331-1248A>T		intron	N/A	NP_000679.1
	ALAS1	NM_001304444.1		c.1382-1248A>T		intron	N/A	NP_001291373.1
	ALAS1	NM_001304443.1		c.1331-1248A>T		intron	N/A	NP_001291372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALAS1	ENST00000484952.6	TSL:1 MANE Select	c.1331-1248A>T		intron	N/A	ENSP00000418779.1
	ALAS1	ENST00000310271.6	TSL:1	c.1331-1248A>T		intron	N/A	ENSP00000309259.2
	ALAS1	ENST00000469224.5	TSL:1	c.1331-1248A>T		intron	N/A	ENSP00000417719.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50605 AN: 151988 Hom.: 9236 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.333 AC: 50621 AN: 152106 Hom.: 9237 Cov.: 32 AF XY: 0.334 AC XY: 24842 AN XY: 74336

African (AFR) AF: 0.176 AC: 7322 AN: 41508

American (AMR) AF: 0.397 AC: 6070 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1584 AN: 3468

East Asian (EAS) AF: 0.358 AC: 1854 AN: 5174

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4818

European-Finnish (FIN) AF: 0.393 AC: 4145 AN: 10558

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26873 AN: 67980

Other (OTH) AF: 0.337 AC: 708 AN: 2104

Alfa AF: 0.231 Hom.: 620

Bravo AF: 0.327

Asia WGS AF: 0.346 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.49
PhyloP100		-0.038
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: rs11712164; hg19: chr3-52244051;