rs17038619

Variant names:

• chr6-34245956-C-T
• rs17038619
• NM_145899.3:c.*1072C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_145899.3(HMGA1):​c.*1072C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000573 in 282,668 control chromosomes in the GnomAD database, including 1 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 0.00050 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (1 hom.)
• Consequence: HMGA1 NM_145899.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 1 publications found

Genes affected

HMGA1 (HGNC:5010): (high mobility group AT-hook 1) This gene encodes a chromatin-associated protein involved in the regulation of gene transcription, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells. The encoded protein preferentially binds to the minor groove of AT-rich regions in double-stranded DNA. Multiple transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene have been identified on multiple chromosomes. [provided by RefSeq, Jan 2016]

HMGA1 Gene-Disease associations (from GenCC):

• type 2 diabetes mellitus

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BS2: High AC in GnomAd4 at 76 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGA1	NM_145899.3	c.*1072C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000311487.9	NP_665906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGA1	ENST00000311487.9	c.*1072C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_145899.3	ENSP00000308227.4

Frequencies

GnomAD3 genomes AF: 0.000499 AC: 76 AN: 152232 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000660 AC: 86 AN: 130318 Hom.: 1 Cov.: 0 AF XY: 0.000801 AC XY: 52 AN XY: 64930

African (AFR) AF: 0.000260 AC: 1 AN: 3842

American (AMR) AF: 0.00 AC: 0 AN: 4216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5710

East Asian (EAS) AF: 0.00 AC: 0 AN: 11172

South Asian (SAS) AF: 0.00147 AC: 18 AN: 12254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 670

European-Non Finnish (NFE) AF: 0.000764 AC: 61 AN: 79880

Other (OTH) AF: 0.000654 AC: 6 AN: 9168

GnomAD4 genome AF: 0.000499 AC: 76 AN: 152350 Hom.: 0 Cov.: 32 AF XY: 0.000362 AC XY: 27 AN XY: 74488

African (AFR) AF: 0.0000481 AC: 2 AN: 41580

American (AMR) AF: 0.000261 AC: 4 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000911 AC: 62 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000117 Hom.: 0

Bravo AF: 0.000438

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		-0.20

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: rs17038619; hg19: chr6-34213733;