rs2780219

Positions:

• chr6-34244966-A-C
• chr6-34244966-A-G
• chr6-34244966-A-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_145899.3(HMGA1):​c.*82A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGA1 NM_145899.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 6-34244966-A-C is Benign according to our data. Variant chr6-34244966-A-C is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 138 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGA1	NM_145899.3	c.*82A>C		3_prime_UTR_variant	6/6	ENST00000311487.9	NP_665906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGA1	ENST00000311487.9	c.*82A>C		3_prime_UTR_variant	6/6	1	NM_145899.3	ENSP00000308227.4

Frequencies

GnomAD3 genomes AF: 0.000934 AC: 136 AN: 145542 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.000874

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000821

Gnomad ASJ AF: 0.000874

Gnomad EAS AF: 0.00167

Gnomad SAS AF: 0.00175

Gnomad FIN AF: 0.00134

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000844

Gnomad OTH AF: 0.00100

GnomAD3 exomes AF: 0.00210 AC: 313 AN: 148880 Hom.: 0 AF XY: 0.00175 AC XY: 139 AN XY: 79476

Gnomad AFR exome AF: 0.00193

Gnomad AMR exome AF: 0.00529

Gnomad ASJ exome AF: 0.00282

Gnomad EAS exome AF: 0.000636

Gnomad SAS exome AF: 0.000845

Gnomad FIN exome AF: 0.000396

Gnomad NFE exome AF: 0.00169

Gnomad OTH exome AF: 0.00549

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00409 AC: 5455 AN: 1334044 Hom.: 0 Cov.: 25 AF XY: 0.00381 AC XY: 2513 AN XY: 659696

Gnomad4 AFR exome AF: 0.00449

Gnomad4 AMR exome AF: 0.00594

Gnomad4 ASJ exome AF: 0.00222

Gnomad4 EAS exome AF: 0.00130

Gnomad4 SAS exome AF: 0.00144

Gnomad4 FIN exome AF: 0.000295

Gnomad4 NFE exome AF: 0.00457

Gnomad4 OTH exome AF: 0.00348

GnomAD4 genome AF: 0.000947 AC: 138 AN: 145656 Hom.: 0 Cov.: 20 AF XY: 0.000932 AC XY: 66 AN XY: 70814

Gnomad4 AFR AF: 0.000897

Gnomad4 AMR AF: 0.000820

Gnomad4 ASJ AF: 0.000874

Gnomad4 EAS AF: 0.00167

Gnomad4 SAS AF: 0.00197

Gnomad4 FIN AF: 0.00134

Gnomad4 NFE AF: 0.000844

Gnomad4 OTH AF: 0.000991

Alfa AF: 0.00851 Hom.: 7571

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.15
DANN	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs2780219; hg19: chr6-34212743; COSMIC: COSV105143077; COSMIC: COSV105143077;